Devices and methods for controlling patient temperature

ABSTRACT

Relatively non-invasive devices and methods for heating or cooling a patient&#39;s body are disclosed. Devices and methods for treating ischemic conditions by inducing therapeutic hypothermia are disclosed. Devices and methods for inducing therapeutic hypothermia through esophageal cooling are disclosed. Devices and methods for operative temperature management are disclosed.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/768,752 filed on Feb. 15, 2013, which is a continuation-in-part ofU.S. patent application Ser. No. 13/609,624 filed on Sep. 11, 2012,which is a continuation-in-part of U.S. patent application Ser. No.13/482,581 filed on May 29, 2012, which is a continuation-in-part ofU.S. patent application Ser. Nos. 13/021,805, 13/021,820, and13/021,828, all filed on Feb. 7, 2011, which were filed as continuationsof U.S. patent application Ser. No. 12/713,644 filed on Feb. 26, 2010,which claims the priority of U.S. Patent Application No. 61/155,876filed on Feb. 26, 2009. The disclosures of each of the aforementionedapplications are hereby incorporated by reference in their entireties.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with Government support under National ScienceFoundation (NSF) Award Number 1142664. The Government has certain rightsin this invention.

BACKGROUND OF THE INVENTION

In industrial countries, 36 to 128 per 100,000 inhabitants per yearexperience a sudden out-of-hospital cardiac arrest (“OHCA”) withsurvival remaining a rare event. Cardiovascular disease affects anestimated 80,700,000 North American adults, with approximately 2400individuals dying from cardiovascular disease daily (an average of onedeath every 37 seconds). Approximately 310,000 coronary heart diseasedeaths due to OHCA occur annually.

According to data reported by the National Registry of CardiopulmonaryResuscitation in 2007, over 75% of patients having cardiopulmonaryarrest events did not survive the event. For those who did survive theevent, an additional 35.2% died afterward.

In the 1950s, moderate hypothermia (body temperature of approximately28° C. to approximately 32° C.) and deep hypothermia (body temperatureof approximately <28° C.) were utilized for various surgical proceduresas well as experimentally to reverse neurological insults associatedwith cardiac arrest. However, because of the numerous complications ofmoderate-to-deep hypothermia and the difficulty in inducing thesetemperature reductions, enthusiasm for the use of therapeutichypothermia waned. Consequently, the use of hypothermia to help reversethe neurologic insult after normothermic cardiac arrest lay dormant forseveral decades. However, beginning in the late 1980s, positive outcomesfollowing cardiac arrest were reported in dogs with mild hypothermia.

Contemporary use of mild therapeutic hypothermia following cardiacarrest in human patients is supported by recent randomized controltrials and a meta-analysis of individual patient data. Majororganizations, including the International Liaison Committee onResuscitation (“ILCOR”) and the American Heart Association (“AHA”),recommend the induction of mild therapeutic hypothermia for comatosecardiac arrest survivors. However, the AHA therapeutic hypothermiaguidelines lack a concrete description of exactly how to cool patients.

Despite widespread support for mild therapeutic hypothermia in thecontext of cardiac arrest, including consensus recommendations frommajor resuscitative organizations, the use of mild therapeutichypothermia in clinical practice remains low. Many clinicians reportthat therapeutic hypothermia is too technically difficult to achieve inpractice.

In addition, health care professionals occasionally need to inducehypothermia during certain surgical procedures or prevent inadvertenthypothermia and the multiple adverse effects that result fromuncontrolled and unintended deviations from normal body temperature.

Control of a patient's body temperature while undergoing surgicalprocedures in the operating room is beneficial because, for instance,even mild inadvertent hypothermia during operative procedures increasesthe incidence of wound infection, prolongs hospitalization, increasesthe incidence of morbid cardiac events and ventricular tachycardia, andimpairs coagulation.

Even mild hypothermia (<1° C.) significantly increases blood loss byapproximately 16% and increases the relative risk for transfusion byapproximately 22%, while maintaining perioperative normothermia reducesblood loss and transfusion requirement by clinically important amounts.

Because considerable strong evidence shows that thermal managementimproves outcomes in a variety of surgical patients, the currentAmerican Heart Association-American College of Cardiology 2007Guidelines on Perioperative Cardiovascular Evaluation and Care forNoncardiac Surgery include a Level 1 recommendation for maintenance ofperioperative normothermia.

Moreover, recognizing the numerous complications of perioperativehypothermia, the American Society of Anesthesiologists (ASA) hasrecently recommended that postoperative temperature become a basis forassessing physician compliance with current guidelines on the preventionof hypothermia.

Although inadvertent operative hypothermia is considered one of the mostpreventable surgical complications, existing methods to control bodytemperature are limited in efficacy, such that the incidence ofinadvertent operative hypothermia for surgical patients can exceed 50%.

Currently available methods to control body temperature include bothnon-invasive and invasive techniques. For example, the most commonlyused techniques developed to induce therapeutic hypothermia includesurface cooling and invasive cooling.

Surface cooling is relatively simple to use, and can be accomplished bythe use of external vests, cooling helmets, circulating cold-waterblankets, cold forced-air blankets, or with less sophisticated methods,such as ice packs and cold-water immersion, but takes between 2 and 8hours to reduce core body temperature. Surface cooling is limited by therate at which cooling can occur, due to the tendency of blood flow to beshunted away from skin and towards the core. External devices, such asvests or blankets, significantly limit access to important patient areasthat are often needed in critical care, such as for catheter placement,and require removal or modification to perform CPR. Surface coolingtechniques such as ice packs limit the precision with which a patient'stemperature can be controlled. Cooling with ice packs and conventionalcooling blankets often results in unintentional overcooling.

For successful induction and maintenance of induced hypothermia andmaintenance of normothermia, shivering, as well as otherthermoregulatory responses, must be addressed. Benefits from cooling maybe offset by negative consequences from shivering. Both pharmacologicaland nonpharmacological methods have been used to control shivering intherapeutic hypothermia, with meperidine offering one pharmacologicchoice that may provide the greatest reduction in the shiveringthreshold, and other effective pharmacological agents beingdexmedetomidine, midazolam, fentanyl, ondansetron, and magnesiumsulfate. As a last resort, neuromuscular blocking agents are consideredappropriate therapy for management of refractory shivering. Skincounterwarming techniques, such as use of an air-circulating blanket,are non-pharmacological methods for reducing shivering when used inconjunction with medication. Nevertheless, treatment for shivering whileavoiding the negative consequences of many anti-shivering therapies isoften difficult.

As another example, several methods are utilized to warm a patient, andinclude raising the operating room temperature and using externalwarming devices, such as forced-air warming blankets.

Several issues exist with these current methods: (1) excessively warmroom temperature creates an uncomfortable environment for the surgicalteam, (2) forced-air warmers are bulky and may impact the surgicalfield; they tend to be inefficient and must be used for extended periodsof time in the operating room, and (3) none of these systems adequatelycontrol or manage temperature, leading to both overheating or, moreoften, inadequate warming.

Rasmussen et al. (Forced-air surface warming versus oesophageal heatexchanger in the prevention of perioperative hypothermia. ActaAnaesthesiol Scand. 1998 March; 42(3):348-52) mention that forced-airwarming of the upper part of the body is effective in maintainingnormothermia in patients undergoing abdominal surgery of at least 2 hexpected duration, while central heating with an esophageal heatexchanger does not suffice to prevent hypothermia. Brauer et al.(Oesophageal heat exchanger in the prevention of perioperativehypothermia. Acta Anaesthesiol Scand. 1998 March; 42(10):1232-33) statesthat an esophageal heat exchanger can only add a small amount of heat tothe overall heat balance of the body.

Invasive temperature management treatments include: the infusion of coldintravenous fluids; the infusion of warmed intravenous fluids; coldcarotid infusions; single carotid artery perfusion with extracorporealcooled blood; cardiopulmonary bypass; ice water nasal lavage; coldperitoneal lavage; nasogastric and rectal lavage; and the placement ofinvasive intravenous catheters connected to refrigerant or heat exchange(warming) devices. Invasive temperature management treatments oftenrequire significant personnel involvement and attention to performsuccessfully. Moreover, certain invasive temperature managementmodalities have been associated with overcooling, overheating, or, moreoften, inadequate warming.

The use of intravenous fluid as a temperature management modality hasthe undesirable effect of contributing to circulating fluid volumeoverload, and has been found to be insufficient for maintaining targettemperature. In addition, large volumes of fluids must be infused toobtain a significant effect.

Other techniques for achieving hypothermia include blood cooling throughinhaled gases and the use of balloon catheters.

However, Andrews et al. (Randomized controlled trial of effects of theairflow through the upper respiratory tract of intubated brain-injuredpatients on brain temperature and selective brain cooling. Br. J.Anaesthesia. 2005; 94(3):330-335) mention that a flow of humidified airat room temperature through the upper respiratory tracts of intubatedbrain-injured patients did not produce clinically relevant orstatistically significant reductions in brain temperature.

Dohi et al. (Positive selective brain cooling method: a novel, simple,and selective nasopharyngeal brain cooling method. ActaNeurochirgurgica. 2006; 96:409-412) mention that a Foley ballooncatheter inserted to direct chilled air into the nasal cavity, when usedin combination with head cooling by electric fans, was found toselectively reduce brain temperature.

Holt et al. (General hypothermia with intragastric cooling. Surg.Gynecol Obstet. 1958; 107(2):251-54; General hypothermia withintragastric cooling: a further study. Surg Forum. 1958; 9:287-91)mention using an intragastric balloon in combination with thermicblankets to produce hypothermia in patients undergoing surgicalprocedures.

Likewise, Barnard (Hypothermia: a method of intragastric cooling. Br. J.Surg. 1956; 44(185):296-98) mentions using an intragastric balloon forinducing hypothermia by intragastric cooling.

US Patent Application Publication 2004/0199229 to Lasheras mentionsheating or cooling via a balloon inserted into a patient's colon.

US Patent Application Publication 2004/0210281 to Dzeng et al. (now U.S.Pat. No. 7,758,623) mentions a transesophageal balloon catheter forspecifically cooling the heart and disparages technologies that cool theentire body.

US Patent Application Publication 2007/0055328 to Mayse et al. mentionsa balloon catheter for protecting the digestive tract of a personundergoing cardiac ablation to correct cardiac arrhythmia.

U.S. Pat. No. 6,607,517 to Dae et al. is generally directed to usingendovascular cooling to treat congestive heart failure.

Several complications are known to result from increasing pressurewithin the gastrointestinal tract, as may occur with a balloon inflatedwithin the stomach, colon, or other gastrointestinal organ. For example,stomach inflation may trigger intestinal rupture, regurgitation andaspiration that may result in pneumonia, esophageal tears, colonnecrosis, and gut ischemia.

In addition, several temperature-controlling modalities, particularlythose that employ inflatable balloons, limit access of the health careprovider to particular anatomical structures that may be crucial forpatient care, such as the stomach. These modalities may require removalor modification to achieve proper treatment.

To date, no available modality for controlling patient temperature hasbeen found that sufficiently overcomes the technical, logistical, andfinancial barriers that exist. The ideal patient temperature controldevice has yet to be developed.

In summary, the state of the art related to the control of patienttemperature comprises at least one significant long felt need: methodsand devices for efficient, safe, and rapid control of patienttemperature while maintaining access to anatomical areas necessary foradditional treatment. The present technology identifies severalindications, diseases, disorders, and conditions that can be treated orprevented by controlling patient temperature and, further, providesrelatively non-invasive methods and devices for rapidly and efficientlycontrolling patient temperature while reducing the risks posed by priordevices and methods. Moreover, certain embodiments of the presenttechnology provide relatively non-invasive methods and devices forrapidly and efficiently controlling patient temperature, while at thesame time maintaining access to important anatomical structures. Certainembodiments of the present technology also provide methods and devicesfor inducing and maintaining mild hypothermia or maintainingnormothermia in a subject without producing thermoregulatory shivering.Certain embodiments of the present technology also provide methods anddevices for maintaining a subject's core body temperature within anarrow range with little variation around the goal temperaturethroughout the steady-state of the treatment protocol. Certainembodiments of the present technology also provide methods and devicesfor efficiently re-warming a subject following induced hypothermia.

BRIEF SUMMARY OF THE INVENTION

At least one aspect of the present technology provides one or moremethods for inducing systemic hypothermia. The methods compriseinserting a heat transfer device, including a fluid path defined by aninflow lumen and an outflow lumen, into a patient's esophagus;initiating flow of a cooling medium along the fluid path; andcirculating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient. The heat transfer device maycomprise a heat transfer region having a splined inner surfacesurrounding the cooling medium flow path. The heat transfer device mayinclude a discrete heat transfer region that is confined to thepatient's esophagus. The patient may be maintained in a state ofhypothermia for at least about two hours, for example. The methods mayfurther comprise monitoring at least one physiological parameter of thepatient, such as body temperature, pressure, oxygen saturation, pH,heart rate, Doppler signals, electromagnetic fluctuations, or chemicalcomposition. For example, the methods may comprise monitoringintra-abdominal compartment pressure or monitoring esophageal pressurethrough a pressure transducer incorporated with the device. The methodsmay further comprise using a lab-on-chip to perform biochemical assays,dielectrophoresis, real-time PCR, and immunoassays for the detection ofbacteria, viruses, and cancers. The methods may further comprisemaintaining the patient's body temperature below about 34° C.

At least one aspect of the present technology provides one or moremethods for controlling core body temperature in a subject. The methodscomprise inserting a heat transfer device, including a fluid pathdefined by an inflow lumen and an outflow lumen, into a subject'sesophagus; initiating flow of a heat transfer medium along the fluidpath; and circulating the medium along the fluid path for a timesufficient to control core body temperature in a subject. The heattransfer device may comprise a heat transfer region having a splinedinner surface surrounding the heat transfer medium flow path. The heattransfer device may include a discrete heat transfer region that isconfined to the patient's esophagus. The core body temperature of thesubject may be controlled for at least about two hours, for example. Themethods may further comprise monitoring at least one physiologicalparameter of the subject, such as body temperature, pressure, oxygensaturation, pH, heart rate, Doppler signals, electromagneticfluctuations, or chemical composition. For example, the methods maycomprise monitoring intra-abdominal compartment pressure or monitoringesophageal pressure through a pressure transducer incorporated with thedevice. The methods may further comprise using a lab-on-chip to performbiochemical assays, dielectrophoresis, real-time PCR, and immunoassaysfor the detection of bacteria, viruses, and cancers. The methods mayfurther comprise maintaining the patient's body temperature, forexample, below about 34° C., between about 34° C. and about 37° C., orat about 37° C.

At least one aspect of the present technology provides one or moreesophageal heat transfer devices. The devices comprise: a plurality oflumens configured to provide a fluid path for flow of a heat transfermedium; a proximal end including an input port and an output port; adistal end configured for insertion into a patient's esophagus. Thedevices may further comprise a hollow tube having a distal endconfigured to extend into the patient's stomach or a more distalcomponent of the gastrointestinal tract, such as the jejunum. The hollowtube can be used to administer medications or alimentation to thegastrointestinal tract. The devices may further comprise ananti-bacterial coating.

At least one aspect of the present technology provides one or moremethods for treating or preventing ischemia-reperfusion injury or injurycaused by an ischemic condition. The methods comprise inserting a heattransfer device, including a fluid path defined by an inflow lumen andan outflow lumen, into a patient's esophagus; initiating flow of acooling medium along the fluid path; and circulating the cooling mediumalong the fluid path for a time sufficient to induce systemichypothermia in the patient. The heat transfer device may comprise asplined inner surface surrounding the cooling medium flow path.

At least one aspect of the present technology provides one or moremethods for treating or preventing neurological or cardiac injury. Themethods comprise inserting a heat transfer device, including a fluidpath defined by an inflow lumen and an outflow lumen, into a patient'sesophagus; initiating flow of a cooling medium along the fluid path; andcirculating the cooling medium along the fluid path for a timesufficient to induce systemic hypothermia in the patient. Theneurological injury may be associated with, for example, stroke(including ischemic stroke), traumatic brain injury, spinal cord injury,subarachnoid hemorrhage, out-of-hospital cardiopulmonary arrest, hepaticencephalopathy, perinatal asphyxia, hypoxic-anoxic encephalopathy,infantile viral encephalopathy, near-drowning, anoxic brain injury,traumatic head injury, traumatic cardiac arrest, newbornhypoxic-ischemic encephalopathy, hepatic encephalopathy, bacterialmeningitis, cardiac failure, post-operative tachycardia, or acuterespiratory distress syndrome (“ARDS”). The heat transfer device maycomprise a splined inner surface surrounding the cooling medium flowpath.

At least one aspect of the present technology provides one or moremethods for treating myocardial infarction, stroke, traumatic braininjury, or ARDS. The methods comprise inducing mild therapeutichypothermia in a patient. Mild therapeutic hypothermia may be inducedvia esophageal cooling. The patient may be maintained in a state ofhypothermia for at least about two hours, for example. The methods mayfurther comprise monitoring at least one physiological parameter of thepatient, such as body temperature, pressure, oxygen saturation, pH,heart rate, Doppler signals, electromagnetic fluctuations, or chemicalcomposition. For example, the methods may comprise monitoringintra-abdominal compartment pressure or monitoring esophageal pressurethrough a pressure transducer incorporated with the device. The methodsmay further comprise using a lab-on-chip to perform biochemical assays,dielectrophoresis, real-time PCR, and immunoassays for the detection ofbacteria, viruses, and cancers. The methods may further comprisemaintaining the patient's body temperature below about 34° C.

At least one aspect of the present technology provides one or moremethods for treating myocardial infarction, stroke, traumatic braininjury, or ARDS. The methods comprise inserting a heat transfer device,including a fluid path defined by an inflow lumen and an outflow lumen,into a patient's esophagus; initiating flow of a cooling medium alongthe fluid path; and circulating the cooling medium along the fluid pathfor a time sufficient to induce systemic hypothermia in the patient. Theheat transfer device may comprise a splined inner surface surroundingthe cooling medium flow path.

At least one aspect of the present technology provides one or moremethods for treating cardiac arrest. The methods comprise inducingsystemic hypothermia via esophageal cooling. The methods may furthercomprise inserting a heat transfer device, including a fluid pathdefined by an inflow lumen and an outflow lumen, into a patient'sesophagus; initiating flow of a cooling medium along the fluid path; andcirculating the cooling medium along the fluid path for a timesufficient to induce systemic hypothermia in the patient. The heattransfer device may comprise a splined inner surface surrounding thecooling medium flow path.

At least one aspect of the present technology provides one or moremethods for operative temperature management. The methods comprisecontrolling a patient's core body temperature via esophageal cooling.The methods may further comprise inserting a heat transfer device,including a fluid path defined by an inflow lumen and an outflow lumen,into a patient's esophagus; initiating flow of a heat transfer mediumalong the fluid path; and circulating the heat transfer medium along thefluid path for a time sufficient to control the patient's core bodytemperature. The methods may further comprise administering medicationsor alimentation to the gastrointestinal tract while simultaneouslycontrolling a patient's core body temperature via esophageal cooling.

At least one aspect of the present technology provides one or moredevices for cooling or warming multiple portions of a patient's bodysimultaneously. The devices comprise a heat transfer device including aproximal end, a distal end, at least one flexible tube extending theproximal and distal end, and additional flexible tubes extending fromthe proximal end. The proximal end includes a heat transfer medium inputport, a heat transfer medium output port, and from about 2 to about 4ancillary tubes extending off the proximal end providing for multipleheat transfer medium flow pathways. The distal end of the device isconfigured for insertion into a larger orifice of a patient, while thedistal ends of the ancillary tubes are configured for insertion intoadditional smaller orifices or configured external as an externalcomponent for surface contact. For example, the ancillary tubes can beconfigured as a head and/or neck wrap to provide surface cooling.

At least one aspect of the present technology provides a heat transferdevice, which may comprise (a) a plurality of lumens configured toprovide a fluid path for flow of a heat transfer medium; (b) a heattransfer region configured for contacting esophageal epithelium,nasopharyngeal epithelium, auricular canal epithelium, and or thetympanic membranes of a patient; (c) a proximal end including an inputport, an output port, and ancillary tubing containing heat transfermedium flow channels; and (d) a distal end configured for insertion intoan esophagus of a patient. The heat transfer device can also comprise ahollow tube having a distal end configured to extend into the patient'sstomach or a more distal component of the gastrointestinal tract, suchas the jejunum. The hollow tube can be used to administer medications oralimentation to the gastrointestinal tract. The heat transfer device canbe capable of contacting substantially all of the patient's esophagealepithelium, nasopharyngeal epithelium, auricular canal epithelium, orthe tympanic membranes.

At least one aspect of the present technology provides one or moredevices for cooling or warming at least one portion of a patient's body.The devices comprise a heat transfer device including a proximal end, adistal end, and at least one flexible tube extending between theproximal and distal end. The proximal end includes a heat transfermedium input port and a heat transfer medium output port. The distal endis configured for insertion into an orifice of a patient. The flexibletube defines an inflow lumen and an outflow lumen and the lumens may beconfigured to provide a fluid path for flow of a heat transfer medium.The heat transfer medium is delivered to a heat transfer region of theheat transfer device via the inflow lumen and removed from the heattransfer region via the outflow lumen. The inflow and outflow lumens maycomprise a part or all of the heat transfer region. A single flexibletube may define both the inflow lumen and the outflow lumen. Forexample, the flexible tube may take on a U-shaped configuration or asubstantially helical configuration such that one portion of the tubedefines the inflow lumen and another portion of the flexible tubedefines the outflow lumen. Alternatively, the same portion of theflexible tube may define the inflow and outflow lumens. For example,heat transfer medium may be delivered to the heat transfer region andextracted from the heat transfer region via the same portion of theflexible tube. In one embodiment, an external pump may alternativelydeliver and withdraw heat transfer medium via a single flexible tube. Inyet another embodiment of the present technology, more than one flexibletube may define the inflow and outflow lumens. For example, two or moretubes may be arranged concentrically such that the lumen of the outertube serves as the inflow lumen and the lumen of the inner tube servesas the outflow lumen. Alternatively, two or more tubes may be arrangedin parallel, with at least one tube defining an inflow lumen and atleast one tube defining an outflow lumen. The lumens of the paralleltubes may be connected such that the heat transfer medium can pass fromthe inflow lumen to the outflow lumen. The flexible tube may comprise asplined inner surface surrounding the heat transfer medium flow path.The devices further comprise a supply line connected to the input portand a return line connected to the output port.

The device may be used to treat or prevent, for example, injury causedby an ischemic condition; ischemia-reperfusion injury; neurologicalinjury; cardiac injury. The device may be used to treat patients whohave experienced or are experiencing myocardial infarction; stroke;traumatic brain injury; or ARDS. The methods of treating or preventingsuch conditions or diseases comprise inserting the distal end of theheat transfer device nasally or orally; advancing the distal end intothe patient's esophagus; initiating flow of a cooling medium along thefluid path; and circulating the cooling medium along the fluid path fora time sufficient to induce systemic hypothermia in the patient. Thepatient may be maintained in a state of hypothermia for at least twohours. The methods may further comprise monitoring at least onephysiological parameter of the patient, such as body temperature,pressure, oxygen saturation, pH, heart rate, Doppler signals,electromagnetic fluctuations, or chemical composition. For example, themethods may comprise monitoring intra-abdominal compartment pressure ormonitoring esophageal pressure through a pressure transducerincorporated with the device. The methods may further comprise using alab-on-chip to perform biochemical assays, dielectrophoresis, real-timePCR, and immunoassays for the detection of bacteria, viruses, andcancers. The methods may further comprise maintaining the patient's bodytemperature below about 34° C.

The device may be used to control a patient's core body temperatureduring, for example, surgical procedures. The methods of controlling thepatient's core body temperature comprise inserting the distal end of theheat transfer device nasally or orally; advancing the distal end intothe patient's esophagus; initiating flow of a heat transfer medium alongthe fluid path; and circulating the heat transfer medium along the fluidpath for a time sufficient to control core body temperature in thepatient. The core body temperature of the subject may be controlled forat least about two hours, for example. The methods may further comprisemonitoring at least one physiological parameter of the subject, such asbody temperature, pressure, oxygen saturation, pH, heart rate, Dopplersignals, electromagnetic fluctuations, or chemical composition. Forexample, the methods may comprise monitoring intra-abdominal compartmentpressure or monitoring esophageal pressure through a pressure transducerincorporated with the device. The methods may further comprise using alab-on-chip to perform biochemical assays, dielectrophoresis, real-timePCR, and immunoassays for the detection of bacteria, viruses, andcancers. The methods may further comprise maintaining the patient's bodytemperature, for example, below about 34° C., between about 34° C. andabout 37° C., or at about 37° C.

At least one aspect of the present technology provides one or moremethods for inducing systemic hypothermia while simultaneously impartinglocal normothermia, for example to the region of the esophagus inclosest proximity to the atrium of the heart.

At least one aspect of the present technology provides an esophagealheat transfer device comprising (a) a plurality of lumens configured toprovide a fluid path for flow of a heat transfer medium; (b) a heattransfer region configured for contacting esophageal epithelium of apatient; (c) a proximal end including an input port and an output port;and (d) a distal end configured for insertion into an esophagus of apatient. The heat transfer device can also comprise a hollow tube havinga distal end configured to extend into the patient's stomach or a moredistal component of the gastrointestinal tract, such as the jejunum. Thehollow tube can be used to administer medications or alimentation to thegastrointestinal tract. The heat transfer device can be capable ofcontacting substantially all of the patient's esophageal epithelium. Theheat transfer device can comprise a semi-rigid material. The heattransfer device can be capable of cooling at a rate of about 1.2° C./hrto about 2.4° C./hr. Alternatively, the heat transfer device can becapable of cooling at a rate of about 1.2° C./hr to about 1.8° C./hr.The heat transfer device can be capable of cooling a mass at a rate ofup to about 700 kJ/hr, and, in particular, at a rate of about 410 kJ/hr.Alternatively, the heat transfer device can be capable of cooling a massat a rate of about 350 kJ/hr to about 530 kJ/hr, and, in particular, ata rate of about 430 kJ/hr. The heat transfer device can include a heattransfer region with a surface area of at least about 100 cm² and, inparticular, a surface area of about 140 cm².

At least one aspect of the present technology provides a system forcooling or warming at least one portion of a patient's body, comprisinga heat transfer device including a proximal end, a distal end, and atleast one semi-rigid tube extending between the proximal and distalends; a supply line; and a return line. The proximal end of the heattransfer device includes a heat transfer medium input port and a heattransfer medium output port. The distal end of the heat transfer deviceis configured for insertion into an orifice of a patient, such as theesophageal lumen. The semi-rigid tube defines an inflow lumen and anoutflow lumen and the lumens are configured to provide a fluid path forflow of a heat transfer medium. The supply line is connected to theinput port and the return line is connected to the output port. The heattransfer device can also comprise a hollow tube having a distal endconfigured to extend into the patient's stomach or a more distalcomponent of the gastrointestinal tract, such as the jejunum. The hollowtube can be used to administer medications or alimentation to thegastrointestinal tract. The heat transfer device can be capable ofcontacting substantially all of the patient's esophageal epithelium. Theheat transfer device can comprise a semi-rigid material. The heattransfer device can be capable of cooling at a rate of about 1.2° C./hrto about 2.4° C./hr. Alternatively, the heat transfer device can becapable of cooling at a rate of about 1.2° C./hr to about 1.8° C./hr.The heat transfer device can be capable of cooling a mass at a rate ofup to about 700 kJ/hr, and, in particular, at a rate of about 410 kJ/hr.Alternatively, the heat transfer device can be capable of cooling a massat a rate of about 350 kJ/hr to about 530 kJ/hr, and, in particular, ata rate of about 430 kJ/hr. The heat transfer device can include a heattransfer region with a surface area of at least about 100 cm² and, inparticular, a surface area of about 140 cm².

At least one aspect of the present technology provides a system forcontrolling core body temperature of a subject, comprising a heattransfer tube insertable within the esophagus of the subject; anexternal heat exchanger containing a heat transfer fluid; a pump forflowing the heat transfer fluid through a circuit within the heattransfer tube; a heat transfer element in contact with the external heatexchanger; a sensor for detecting a parameter and generating a signalrepresentative of the parameter, wherein the signal is transmitted to amicroprocessor to control (i) the flow of heat transfer fluid within thecircuit or (ii) the temperature of the heat transfer fluid. The tube isconfigured to contact the epithelial lining of the subject's esophagus.The sensor can be a temperature sensor positioned distal to the heattransfer tube and configured to generate a signal representing the corebody temperature of the subject. The microprocessor can receive a targettemperature input and responds to the signal from the temperature sensorwith a proportional integrated differential response to control the rateat which the subject approaches the target temperature. The sensor canbe a bubble detector and configured to generate a signal representingthe presence of air in the circuit. The heat transfer device can alsocomprise a hollow tube having a distal end configured to extend into thepatient's stomach or a more distal component of the gastrointestinaltract, such as the jejunum. The hollow tube can be used to administermedications or alimentation to the gastrointestinal tract. The heattransfer device can be capable of contacting substantially all of thepatient's esophageal epithelium. The heat transfer device can comprise asemi-rigid material. The heat transfer device can be capable of coolingat a rate of about 1.2° C./hr to about 2.4° C./hr. Alternatively, theheat transfer device can be capable of cooling at a rate of about 1.2°C./hr to about 1.8° C./hr. The heat transfer device can be capable ofcooling a mass at a rate of up to about 700 kJ/hr, and, in particular,at a rate of about 410 kJ/hr. Alternatively, the heat transfer devicecan be capable of cooling a mass at a rate of about 350 kJ/hr to about530 kJ/hr, and, in particular, at a rate of about 430 kJ/hr. The heattransfer device can include a heat transfer region with a surface areaof at least about 100 cm² and, in particular, a surface area of about140 cm².

At least one aspect of the present technology provides a system forcontrolling core body temperature of a subject. The system comprises aheat transfer device having an inflatable heat transfer region, which isinsertable within the esophagus the subject and, upon inflation, atleast partially restricts gastric ventilation. The system also comprisesan external heat exchanger containing a heat transfer fluid; a pump forflowing the heat transfer fluid through a circuit within the heattransfer device; and a heat transfer element in contact with theexternal heat exchanger. The system also comprises a sensor fordetecting a parameter and generating a signal representative of theparameter, wherein the signal is transmitted to a microprocessor tocontrol (i) the flow of heat transfer fluid within the circuit or (ii)the inflation pressure of the inflatable heat transfer region. Theinflatable heat transfer region is configured to contact the epitheliallining of the subject's esophagus upon inflation. The inflatable heattransfer region can be capable of contacting substantially all of thepatient's esophageal epithelium upon inflation. The sensor can be apressure sensor positioned, for example, distal to the inflatable heattransfer region and configured to generate a signal representing theintra-abdominal, gastric or esophageal pressure of the subject. Themicroprocessor can receive a maximum pressure determined by a healthcare professional and respond to the signal from the pressure sensorwith a proportional integrated differential response to control (i) theflow of heat transfer fluid within the circuit or (ii) the inflationpressure of the inflatable heat transfer region. The response generatedby the microprocessor is designed to alleviate the pressure built up inthe gastro-intestinal tract. For example, reducing the flow of heattransfer fluid within the circuit will cause the inflatable heattransfer region to partially or fully deflate, thereby allowing forgastric ventilation. Alternatively, the microprocessor may directlycontrol the inflation pressure of the inflatable heat transfer region.Following gastric ventilation, the microprocessor, for example,generates and sends a signal to increase pump output or otherwisere-inflate the inflatable heat transfer region, thereby at leastpartially restricting gastric ventilation.

At least one aspect of the present technology provides systems andmethods for preventing the negative effects of elevations in gastricpressure associated with an esophageal heat transfer device having aninflatable heat transfer region that, upon inflation, at least partiallyrestricts gastric ventilation. For example, a microprocessor mayperiodically deflate the inflatable heat transfer region by altering theflow of a heat transfer fluid to the inflatable heat transfer region ofthe device. Periodic deflation of the inflatable heat transfer regionwould allow for gastric ventilation. As another example, a pressuresensor for detecting intra-abdominal, gastric or esophageal pressure isincorporated with an esophageal heat transfer device having aninflatable heat transfer region that, upon inflation, at least partiallyrestricts gastric ventilation. Information representing intra-abdominal,gastric or esophageal pressure can be communicated to a microprocessorcapable of inflating or deflating the inflatable heat transfer region.The microprocessor may control inflation or deflation of the inflatableheat transfer region by, for example, altering the flow of a heattransfer fluid to the inflatable heat transfer region of the device. Thepressure sensor may be located distal to the inflatable heat transferregion.

At least one aspect of the present technology provides an esophagealheat transfer device comprising: one or more lumens providing a fluidpath for flow of a heat transfer medium; a distal end configured forinsertion into a pharyngeal opening; a heat transfer region, wherein theheat transfer region is capable of directly contacting esophagealepithelium upon insertion into a patient; a heat transfer medium inputport positioned proximal to the heat transfer region; a heat transfermedium output port positioned proximal to the heat transfer region; anda gastric tube.

In certain embodiments, the one or more lumens provide a fluid path forflow of heat transfer medium. The one or more lumens may comprise aninflow lumen and an outflow lumen. The gastric tube may be arranged inparallel to the inflow lumen or the outflow lumen. Alternatively, thegastric tube may be positioned within the inflow lumen or the outflowlumen.

In other embodiments, a single lumen provides the fluid path for flow ofthe heat transfer medium. The gastric tube may be arranged in parallelto the single lumen. Alternatively, the gastric tube may be positionedwithin the single lumen.

The heat transfer region, or a portion thereof, may be substantiallyhelical. The substantially helical configuration creates an interiorspace defined by the helix, which may comprise a gastric access lumen.In certain embodiments, the gastric tube can be positioned within thegastric access lumen.

At least one aspect of the present technology provides an esophagealheat transfer device comprising: an inflow lumen connected to a heattransfer medium input port; a heat transfer region, wherein the heattransfer region is capable of directly contacting esophageal epitheliumupon insertion into a patient; an outflow lumen connected to a heattransfer medium output port; a distal end configured for insertion intoa nostril or mouth of a patient; and wherein the device is capable ofreceiving a separate gastric tube or gastric probe.

In certain embodiments, the device also comprises a gastric access tubecapable of receiving the separate gastric tube or gastric probe. Thegastric access tube may be arranged in parallel to the inflow lumen orthe outflow lumen. Alternatively, the gastric access tube may bepositioned within the inflow lumen or the outflow lumen.

In yet other embodiments, the heat transfer region, or a portionthereof, of the heat transfer device may be substantially helical. Thesubstantially helical configuration creates an interior space defined bythe helix, which may comprise a gastric access lumen. The gastric tubecan be positioned within the gastric access lumen.

At least one aspect of the present technology provides an esophagealheat transfer device comprising: a distal end configured for insertioninto a nostril or mouth of a patient; a heat transfer region, whereinthe heat transfer region is capable of directly contacting esophagealepithelium upon insertion into the patient; and a gastric tube. Thedevice is capable of receiving a heat transfer medium, such as a gas,liquid, solid, slurry, or gel.

The heat transfer region, or a portion thereof, may be substantiallyhelical. The substantially helical configuration creates an interiorspace defined by the helix, which may comprise a gastric access lumen.In certain embodiments, the gastric tube can be positioned within thegastric access lumen.

In certain embodiments, the present technology includes a system forcontrolling core body temperature. The system comprises a heat transferdevice having an input port capable of receiving a heat transfer mediumfrom an external source and a lumen that is connected to the input portand provides a fluid path for flow of the heat transfer medium to aninflatable heat transfer region. Upon inflation, the inflatable heattransfer region may be capable of contacting the patient's esophagealepithelium. The system also comprises a microprocessor coupled to theexternal source. The microprocessor is capable of regulating the flow ofthe heat transfer medium to the heat transfer region. The microprocessormay also be capable of receiving a target pressure determined by ahealth care professional. The microprocessor may be capable ofperiodically increasing or decreasing the flow of the heat transfermedium to the heat transfer region. The system may also comprise apressure sensor for detecting gastric pressure and generating a signalrepresentative of gastric pressure. The pressure sensor may be capableof sending the signal to the microprocessor. The microprocessor may becapable of increasing or decreasing the flow of the heat transfer mediumto the heat transfer region in response to the signal received from thepressure sensor. The microprocessor may be capable of responding to thesignal from the pressure sensor with a proportional integrateddifferential response to control the flow of the heat transfer medium tothe heat transfer region.

In certain embodiments, the present technology includes a method forcontrolling core body temperature. The method may comprise increasing,decreasing, or maintaining core body temperature. In certain embodimentsthe method comprises the steps of: nasally or orally inserting anesophageal heat transfer device into the patient. The heat transferdevice includes an input port capable of receiving a heat transfermedium from an external source. The heat transfer device also includesan inflatable heat transfer region configured for contacting a patient'sesophageal epithelium upon inflation. The heat transfer device alsoincludes at least one lumen connected to the input port, which providesa fluid path for flow of the heat transfer medium from the input port tothe inflatable heat transfer region. The method also comprises advancingthe inflatable heat transfer region of the heat transfer device into thepatient's esophagus. The method also comprises initiating flow of a heattransfer medium along the fluid path to inflate the inflatable heattransfer region; subsequently deflating the inflatable heat transferregion to permit gastric ventilation; and then re-inflating theinflatable heat transfer region. The method may also comprise the stepof monitoring gastric pressure. Information representing gastricpressure may be communicated to a microprocessor capable of inflating ordeflating the inflatable heat transfer region. The microprocessor may becapable of receiving a target pressure determined by a health careprofessional. The microprocessor may be capable of responding to thesignal from the pressure sensor with a proportional integrateddifferential response to control the flow of the heat transfer medium tothe heat transfer region. The method may also comprise the steps ofmaintaining the core body temperature of the patient at about 36° C. forat least two hours, for at least twenty four hours, or for at leastseventy two hours. The method may also comprise the steps of maintainingthe core body temperature of the patient below about 34° C. for at leasttwo hours, for at least twenty four hours, or for at least seventy twohours. The method may also comprise the steps of maintaining the corebody temperature of the patient at about 33° C. for at least two hours,for at least twenty four hours, or for at least seventy two hours.

In certain embodiments, the present technology includes a method forcontrolling core body temperature. The method may comprise increasing,decreasing, or maintaining core body temperature. In certain embodimentsthe method comprises the steps of: nasally or orally inserting anesophageal heat transfer device into the patient. The heat transferdevice includes an inflatable heat transfer region configured forcontacting a patient's esophageal epithelium upon inflation. The heattransfer device also includes at least one lumen, which provides a fluidpath for flow of the heat transfer medium to the inflatable heattransfer region. The method also comprises advancing the inflatable heattransfer region of the heat transfer device into the patient'sesophagus. The method also comprises initiating flow of a heat transfermedium along the fluid path to inflate the inflatable heat transferregion. Following inflation of the inflatable heat transfer region,gastric access is maintained. The method may also comprise nasally ororally inserting a gastric tube into the patient while the inflatableheat transfer region is in its inflated state. The inflatable heattransfer region may take on a substantially helical shape or asubstantially hourglass shape upon inflation.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a schematic view of a heat transfer system according to anexemplary embodiment of the present technology.

FIG. 2 depicts a heat transfer device according to an exemplaryembodiment of the present technology.

FIG. 3A shows a schematic view of a heat transfer device according to anexemplary embodiment of the present technology. FIG. 3B shows a top downview of a heat transfer device according to an exemplary embodiment ofthe present technology. FIG. 3C shows a cross-sectional view of a heattransfer device according to an exemplary embodiment of the presenttechnology.

FIG. 4 shows a schematic view of a proximal end of a heat transferdevice according to an exemplary embodiment of the present technology.

FIG. 5A shows a schematic view of a distal end of a heat transfer deviceaccording to an exemplary embodiment of the present technology. FIGS.5B-5Q show several cross-sectional views and corresponding schematicviews of a distal end of a heat transfer device according to anexemplary embodiment of the present technology.

FIG. 6A of a heat transfer device according to an exemplary embodimentof the present technology. FIG. 6B shows a longitudinal view and across-sectional view of a heat transfer device according to an exemplaryembodiment of the present technology.

FIG. 7 is a schematic diagram of a distal end of a heat transfer deviceaccording to an exemplary embodiment of the present technology.

FIGS. 8A and 8B show schematic views of a heat transfer device accordingto an exemplary embodiment of the present technology. FIGS. 8C and 8Dshow cross-sectional views of a heat transfer device according to anexemplary embodiment of the present technology.

FIG. 9A is a perspective view of a portion of an exemplary heat transferdevice. FIG. 9B is a longitudinal front side view of a portion of anexemplary heat transfer device. FIG. 9C is a bottom side view of aportion of an exemplary heat transfer device. FIG. 9D is a horizontalfront side view of a portion of an exemplary heat transfer device.

FIG. 10 is a graph depicting the cooling achieved with an exemplarycooling device according to an embodiment of the present technology.

FIG. 11 is a graphed comparison of the rate of cooling achieved by aheat transfer device of the present technology as compared to the rateof cooling demonstrated in US Patent Application Publication2004/0210281 to Dzeng et al.

FIG. 12 is a graph showing the total amount of heat transferred duringthe warming and maintenance phase of the experiment.

FIG. 13 is a temperature plot depicting temperature modulation achievedwith an exemplary cooling device according to an embodiment of thepresent technology.

DETAILED DESCRIPTION OF THE INVENTION

The present technology provides relatively non-invasive devices andmethods for heating or cooling a patient's entire body. The presenttechnology also provides devices and methods for treating ischemicconditions by inducing therapeutic hypothermia. Another aspect of thepresent technology provides devices and methods for inducing therapeutichypothermia through esophageal cooling. The present applicationdemonstrates that heat transfer devices and methods of the presenttechnology achieve unexpectedly-greater rates of temperature change ascompared to other devices and methods and, in particular, thosementioned in US Patent Application Publication 2004/0210281 to Dzeng etal. (now U.S. Pat. No. 7,758,623).

The present technology provides devices and methods for treatingpatients suffering from various diseases and disorders by inducing mildtherapeutic hypothermia (target temperature: about 32° C. to about 34°C.) and maintaining normothermia (target temperature: about 37° C.). Inparticular, mild therapeutic hypothermia may be induced to treatpatients suffering from ischemia or conditions related to ischemia.Without being bound by any particular theory, it is believed thatseveral molecular and physiological responses associated with theischemia-reperfusion cascade, including, for example, glutamate release,stabilization of the blood-brain barrier, oxygen radical production,intracellular signal conduction, protein synthesis, ischemicdepolarization, reduced cerebral metabolism, membrane stabilization,inflammation, activation of protein kinases, cytoskeletal breakdown, andearly gene expression, are sensitive to intra- and post-ischemictemperature reductions. In particular, mild therapeutic hypothermia mayminimize the formation of several metabolic mediators such as freeradicals and suppress the inflammatory response associated withischemia-reperfusion. Moreover, with respect to neurological outcomes,mild therapeutic hypothermia may blunt the cerebral pro-inflammatoryresponse, decrease the production of excitatory mediators of braininjury, such as excitatory amino acids and monoamines, decrease thecerebral metabolic rate, and decrease intracranial pressure. On theother hand, inadvertent hypothermia during operative procedures canreduce platelet function, impair enzymes of the coagulation cascade,enhance anesthetic drug effects, contribute to coagulopathy, increasecardiac demand, and increase the incidence of surgical wound infections.

Certain embodiments of the present technology provide devices andmethods for inducing mild therapeutic hypothermia to treat individualswho have experienced myocardial infarction, stroke, traumatic braininjury, ARDS, hemorrhagic shock, subarachnoid hemorrhage (“SAH”),including non-traumatic aneurysmal SAH, neonatal encephalopathy,perinatal asphyxia (hypoxic ischemic encephalopathy), spinal cordinjury, meningitis, near hanging and near drowning. Without being boundby any particular theory, it is believed that mild therapeutichypothermia may prevent, reduce, or ameliorate neurological, or other,damage associated with the above-mentioned conditions. Additionalembodiments of the present technology provide devices and methods forinducing mild therapeutic hypothermia to treat individuals who haveexperienced metabolic acidosis, pancreatitis, malignant hyperthermia,liver failure and hepatic encephalopathy. Additional embodiments of thepresent technology provide devices and methods for controlling patienttemperature during any general surgical procedure. As used herein, theterm “controlling patient temperature” refers to a patient's core bodytemperature and includes lowering core body temperature, maintainingcore body temperature, raising core body temperature, inducinghypothermia, maintaining normothermia, and inducing hyperthermia.

Certain embodiments of the present technology provide devices andmethods for improving cardiac output, particularly duringcardiopulmonary resuscitation (CPR). Without wishing to be bound by anyparticular theory, it is believed that certain esophageal heat transferdevices of the present technology add support to the medial aspect ofthe heart, which helps reinforce the compression of the heart during thedown stroke of CPR. Placement of such a device during CPR increasescardiac output and blood flow to the brain during a crucial time, whichwould likely confer a survival benefit.

Certain embodiments of the present technology provide for controllingpatient temperature through esophageal warming or cooling. As anexample, a heat transfer agent may be circulated through a heat transferdevice positioned in the patient's esophagus. In certain embodiments,the heat transfer portion of the device is confined to the patient'sesophagus. In certain embodiments, the heat transfer device is incontact with substantially all of the epithelial surface of thepatient's esophagus. The heat transfer device may include a balloon orpartially inflatable lumen. For example, the heat transfer region of theheat transfer device may include an inflatable or partially inflatablelumen. Prior to insertion of the device into a patient, the inflatableor partially inflatable lumen may be in the deflated state. Uponinsertion of the device into a patient, the inflatable or partiallyinflatable lumen may be inflated. As described herein, the inflatable orpartially inflatable lumen may comprise an inflow and an outflow lumen,thereby providing a fluid path for the flow of a heat transfer medium.

In certain embodiments, the heat transfer device may include a balloonor partially inflatable lumen and permit gastric access. In certainembodiments, the heat transfer device further comprises a tube allowingfor gastric access and, for example, gastric suctioning. In oneembodiment, the inflatable or partially inflatable lumen, whichcomprises the heat transfer region, is arranged concentrically with thegastric access tube. For example, the inflatable or partially inflatablelumen may partially or fully surround the gastric access tube. Inanother embodiment, the inflatable or partially inflatable lumen, whichcomprises the heat transfer region, is arranged in parallel with thegastric access tube. For example, the inflatable or partially inflatablelumen may run alongside the gastric access tube. In yet anotherembodiment, the inflatable or partially inflatable lumen, whichcomprises the heat transfer region, is helically wrapped around thegastric access tube. Thus, the heat transfer region, or a portionthereof, may be substantially helical. The substantially helicalconfiguration creates an interior space defined by the helix, withinwhich the gastric access tube may be located. In certain otherembodiments, the heat transfer device comprises a balloon or partiallyinflatable lumen that is capable of inflating so as to permit gastricaccess even when in the inflated state. For example, an inflatable orpartially inflatable lumen may be manufactured such that, uponinflation, the esophagus is not completely occluded. The inflatable orpartially inflatable lumen may take on an hourglass or barbell shapeupon inflation. Alternatively, the inflatable or partially inflatablelumen may take on a helical shape upon inflation, such that gastricaccess is permitted along the axis of the helix.

As another example, inflation of the inflatable or partially inflatablelumen may be guided by a strut, boss, ring, or net to restrict theorientation of the lumen upon inflation, thereby permitting gastricaccess even when the lumen is in the inflated state. The strut, boss,ring, net, or other structure for restricting the orientation of thelumen upon inflation may be affixed to, for example, the outer surfaceof a tube defining an inflow lumen. In operation, a heat transfer mediumwould flow through the inflow lumen into the inflatable or partiallyinflatable lumen, thereby causing the inflatable or partially inflatablelumen to inflate. The structure for restricting the orientation of thelumen upon inflation prevents the inflatable or partially inflatablelumen from completely occluding the esophagus. In certain embodiments,the inflow lumen and the inflatable or partially inflatable lumen arecoextensive.

Alternatively, in certain embodiments of the present invention, the heattransfer portion of the heat transfer device does not include a balloonor partially inflatable lumen.

In operation, heat can be transferred to the esophagus from the heattransfer agent, resulting in an increase in the temperature of theesophagus, as well as adjacent organs or structures, including theaorta, right atrium, vena cavae, and azygos veins, and ultimately,systemic normothermia, or heat can be transferred from the esophagus tothe heat transfer agent, resulting in a decrease in the temperature ofthe esophagus, as well as adjacent organs or structures, including theaorta, right atrium, vena cavae, and azygos veins, and ultimately,systemic hypothermia.

Certain other embodiments of the present technology provide forcontrolling patient temperature through esophago-gastric heat transfer.As an example, a heat exchange medium may be circulated through a heattransfer device of sufficient length such the heat transfer portion ofthe device extends from the patient's esophagus to the patient'sstomach. In certain embodiments, the heat transfer device is in contactwith substantially all of the epithelial surface of the patient'sesophagus. The heat transfer device may include a balloon or partiallyinflatable lumen. Alternatively, in certain embodiments of the presentinvention, the heat transfer portion of the device does not include aballoon or partially inflatable lumen. Employing such anesophago-gastric temperature control device to modulate patienttemperature provides increased surface area for heat transfer andthereby results in more efficient and more rapid temperature management.

At least one aspect of the present technology provides one or moremethods for therapeutic temperature modulation in a subject. Therapeutictemperature modulation encompasses, for example, both mild hypothermiaand the maintenance of normothermia. In certain embodiments, the methodsfor therapeutic temperature modulation comprise controlling core bodytemperature in a subject. The methods comprise inserting a heat transferdevice, which includes a heat transfer region comprising a fluid pathdefined by an inflow lumen and an outflow lumen, into a subject;initiating flow of a heat transfer medium along the fluid path; andcirculating the medium along the fluid path for a time sufficient tocontrol core body temperature in a subject. In certain embodiments, theheat transfer region of the heat transfer device can be inserted into asubject's esophagus. In certain embodiments, the present applicationprovides methods for therapeutic temperature modulation that do notrequire concomitant administration of muscular paralysis medications orother medications commonly utilized to treat shivering (such asmeperidine, dexmedetomidine, midazolam, fentanyl, ondansetron, ormagnesium sulfate).

At least one aspect of the present technology provides one or moreesophageal heat transfer devices. The devices comprise: a heat transferregion configured for placement in a subject's esophagus. The heattransfer region comprises a plurality of lumens configured to provide afluid path for flow of a heat transfer medium. In certain embodiments,the heat transfer region of the heat transfer devices can be capable ofcontacting substantially all of the patient's esophageal epithelium. Thedevices may further comprise a gastrointestinal access tube providingaccess to a more distal component of the gastrointestinal tract, such asthe stomach or jejunum. The gastrointestinal access tube can be used to,for example, remove the contents of the subject's stomach. In certainembodiments, esophageal heat transfer devices of the present technologyare capable of being used to provide therapeutic temperature modulationin a subject without producing thermoregulatory shivering. Withoutwishing to be bound by any particular theory, the benefits of suchdevices may be related to the ability to focus heat transfer at the coreof a patient away from more sensitive skin receptors thought to beactive in generation of the shivering reflex; the increased contactsurface between the heat transfer region of the heat transfer device andthe patient's anatomy; the superior heat transfer characteristics of thematerials used to construct the heat transfer devices of the presenttechnology; and/or the reduction of gastric pressure through gastricventilation.

In certain embodiments, esophageal heat transfer devices of the presenttechnology are capable of maintaining a subject's core body temperaturewithin a narrow range with little variation around the goal temperaturethroughout the steady-state of the treatment protocol. In someembodiments, the range is about ±1° C. of goal temperature. In otherembodiments, the range is about ±0.5° C. of goal temperature. In stillother embodiments, the range is about ±0.1° C. of goal temperature.Without wishing to be bound by any particular theory, such tight controlof a subject's core body temperature during the steady-state of thetreatment protocol may be related to a focus of heat transfer at thecore of a patient where a rich and abundant vascular flow provides anoptimal environment to control a patient's temperature rapidly andefficiently; the increased contact surface between the heat transferregion of the heat transfer device and the patient's anatomy; thesuperior heat transfer characteristics of the materials used toconstruct the heat transfer devices of the present technology; and/orthe reduction of gastric pressure through gastric ventilation.

Certain embodiments of the present technology provide for inducing mildtherapeutic hypothermia by, for example, esophageal cooling, to treatindividuals who have experienced cardiac arrest, includingcocaine-induced cardiac arrest, traumatic cardiac arrest, and cardiacarrest due to non-coronary causes.

Still other embodiments of the present technology provide forcontrolling patient temperature through cooling or warming of apatient's nasopharynx, tympanic membrane, auricular canal, bladder,colon, rectum, or other anatomical structure. As an example, a heatexchange medium may be circulated through a heat transfer devicepositioned in the patient's bladder, colon, rectum, or other anatomicalstructure.

Certain embodiments of the present technology provides for a heattransfer system for heating or cooling a patient. The heat transfersystem may include a heat transfer device, a heat exchanger, a heattransfer medium, and a network of tubular structures for circulating theheat transfer medium between the heat transfer device and the heatexchanger. In other embodiments, the heat transfer system includes aheat transfer device, a chiller, a coolant and a network of tubularstructures for circulating the coolant between the heat transfer deviceand the chiller. In still other embodiments, the heat transfer systemcan be used to cool and subsequently re-warm the patient, as well asmaintain the patient at a predetermined maintenance temperature.

In certain embodiments of the present technology, the heat transferdevice comprises a distal end, a proximal end, and one or more lengthsof tubing extending therebetween. The proximal end of the heat transferdevice includes an input port for receiving a heat transfer medium fromthe heat exchanger and an output port allowing the heat transfer mediumto return to the heat exchanger. The tubing extending from approximatelythe proximal end of the heat transfer device to approximately the distalend of the heat transfer device may include a heat transfer mediumsupply tube and a heat transfer medium return tube. The heat transfermedium supply tube and heat transfer medium return tube may be arranged,for example, in parallel or concentrically. In one non-limiting example,the heat transfer medium return tube is positioned within a lumendefined by the heat transfer medium supply tube. In another non-limitingexample, the heat transfer medium supply tube is positioned within alumen defined by the heat transfer medium return tube. The lumens of theheat transfer medium supply tube and heat transfer medium return tubemay be in fluid communication such that the heat transfer medium mayflow along a fluid path defined by the lumens of the heat transfermedium supply tube and heat transfer medium return tube. In certainembodiments, the flow rate of the heat transfer medium along the fluidpath can be sufficient to prevent significant fluctuations in thetemperature of the heat transfer medium as it flows along the fluidpath. For example, the flow rate of the heat transfer medium can be fromabout 50 mL/min to about 1000 mL/min, preferably about 750 mL/min. Asanother example, the flow rate of the heat transfer medium can besufficient to maintain the temperature of the heat transfer mediumwithin about ±3° C., within about ±2° C., within about ±1° C., or withinabout ±0.5° C. between inlet and outlet temperature. In someembodiments, the flow rate of the heat transfer medium can be sufficientto maintain the temperature of the heat transfer medium within about±0.1° C. between inlet and outlet temperature.

The thickness of the walls of the heat transfer medium supply tubeand/or heat transfer medium return tube contributes to the heat transferresistance of the device. Thus, in certain embodiments, it is preferablefor the heat transfer medium supply tube and/or heat transfer mediumreturn tube to have thin walls. For example, the wall of the heattransfer medium supply tube and/or heat transfer medium return tube maybe less than about 1 millimeter. Alternatively, the wall of the heattransfer medium supply tube and/or heat transfer medium return tube maybe less than about 0.01 millimeter. In some embodiments, the wall of theheat transfer medium supply tube and/or heat transfer medium return tubemay be less than about 0.008 millimeters. As will be appreciated by oneof skill in the art, the thickness of the walls of the heat transfermedium supply tube and/or heat transfer medium return tube may bemodified in increments of about 0.001 millimeters, about 0.01millimeters, or about 0.1 millimeters, for example.

In certain embodiments, heat transfer devices of the present technologyinclude heat transfer regions that, for example, employ splined innersurfaces surrounding the heat exchange medium flow paths. The splinedinner surfaces help to enhance the likelihood of maintenance of laminarflow, and reduce the likelihood of flow obstruction at the point ofcurvature of the oropharynx. Heat transfer devices comprising splinedinner surfaces surrounding the heat exchange medium flow paths providean unexpectedly superior rate of temperature change relative to otherdevices and methods. While not wishing to be bound by any particulartheory, it is thought that heat transfer devices comprising splinedinner surfaces surrounding the heat exchange medium flow paths transfermore heat per unit time than other devices.

In certain embodiments, heat transfer devices of the present technologyinclude a heat transfer region having a substantially helicalconfiguration. For example, the heat transfer region may comprise ahelical tube. The tube may comprise any material described herein,including, for example, a semi-rigid plastic, such as ethylenetetrafluoroethylene (ETFE), polytetrafluoroethylene (PTFE),perfluoroalkoxy (PFA), and fluorinated ethylene propylene (FEP), asemi-rigid elastomer, such as silicone, or an inflatable or partiallyinflatable material, such as a balloon. The tube defines a lumen, which,in some embodiments, provides a fluid path for the flow of a liquid orgaseous heat transfer medium. For example, the tube and correspondinglumen may serve as the evaporative component of a freon/gas circuit andbe connected with an external condenser. In an alternative embodiment,the tube defines a lumen, which is capable of receiving a solid orsemi-solid heat transfer medium.

A helical arrangement of the heat transfer region, or a portion thereof,allows for access to anatomical sites beyond the placement of the heattransfer device. The substantially helical configuration of the tubecreates an interior space defined by the helix, which may comprise, forexample, an access lumen. In some embodiments, the helical heat transferregion, or portion thereof, defines an access lumen. For example, wherethe heat transfer device is for placement within the esophagus, thehelical heat transfer region, or portion thereof, allows for gastricaccess via a gastric access lumen. A separate probe, such as atemperature probe, or separate tube, such as a nasogastric tube or anorogastric tube, can be inserted into the patient via the gastric accesslumen. The nasogastric tube, orogastric tube, or probe may be providedwith the heat transfer device or provided as an after-market component.

The manufacture of heat transfer devices of the present technology isrelatively inexpensive. For example, an esophageal heat transfer devicecan be constructed using an elastomer such as biomedical grade extrudedsilicone rubber, and an adhesive. Commercially available elastomers andadhesives include, for example, Dow Corning Q7 4765 silicone and NusilMed2-4213. The low cost and ease of use of such materials is expected tolead to widespread adoption of the esophageal heat transfer devices ofthe present technology.

In certain embodiments, the heat transfer device, including, forexample, the supply tube, may comprise a semi-rigid material, such as asemi-rigid plastic, including ethylene tetrafluoroethylene (ETFE),polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA), and fluorinatedethylene propylene (FEP), or a semi-rigid elastomer, such as silicone. Aheat transfer device comprising a supply tube constructed of asemi-rigid material is easier to place into a patient's esophagus than,for example, a flexible, balloon-type device. In particular, a heattransfer device comprising a flexible material, such as a balloon,requires a delivery device, such as a catheter, guide wire, or sleeve,to direct the heat transfer device into the patient's esophagus.Moreover, flexible, expandable material like a balloon is susceptible tofailures, such as bursting, splitting, or puncturing. Use of asemi-rigid material in the construction of a heat transfer device,reduces the points of failure associated with balloon-type device.

In certain embodiments a rigid sleeve may be employed to guide the heattransfer device during placement into a patient. The rigid sleeve mayhave a section cut-out such that the sleeve comprises approximately asemi-circle in cross section. The sleeve may be removed by sliding itproximally off the heat transfer device. Such a sleeve has certainbenefits over a centrally placed guide wire, including a reduced rate ofcomplications from using a guide wire, such as loss of the guide wireinto the body cavity and damage caused by the guide wire itself.

In other embodiments, an esophageal heat transfer device of the presenttechnology possesses advantages over other temperature managementmodalities in that no additional devices, such as stylets, orcomplicated techniques, such as freezing of the tube, are required forobtaining successful placement in the patient. For example, placement oftraditional gastric tubes in an anesthetized, paralyzed, and intubatedpatient can sometimes be difficult, and many methods have been proposedto aid in the procedure when difficulties occur, including freezing ofthe tubes, using malleable metal stylets, and the use of slipknots onintubating stylets. Such methods are cumbersome and complicated becauseadditional devices and/or steps are required. In some cases, gastrictubes made of nonreinforced polymer plastic materials can be prone tokinking and coiling during insertion. The ability to place a gastrictube in a relatively simple manner without requiring additional devicesor complicated techniques represents a problem that is not solved bymethods such as tube freezing and/or the use of malleable metal styletsor slipknots on intubating stylets. Certain embodiments of the presenttechnology provide methods and devices for placement of a gastric tubewithout requiring additional devices or complicated techniques.

A heat transfer device of the present technology may be placed easily inthe patient without additional devices or complicated techniques, bysimply connecting the device to the external heat exchanger, turning onthe external heat exchanger, and allowing the natural flow of heatexchange medium to provide sufficient firmness to the heat transferdevice to allow simple placement.

An esophageal heat transfer device of the present technology isportable, relatively easy to use, and can be inserted into a patient'sesophagus by a single health care provider, including a nurse, certifiedfirst responder, paramedic, emergency medical technician, or otherpre-hospital or in-hospital care provider. An esophageal heat transferdevice of the present technology possesses advantages over devices thatrequire multiple people and/or a person trained in advanced medicalcare. In addition, in a surgical setting, for example, an esophagealheat transfer device of the present technology possesses advantages overother temperature management modalities in that less personnel andattention is required to insert, employ, and/or monitor an esophagealheat transfer device.

For example, users of a balloon-type device must guard against over- orunder-inflation of the balloon. Over-inflation can lead to undesiredoutcomes, including pressure necrosis. Under-inflation can reduce theability of the device to transfer heat to/from the patient. The use of aballoon-type heat transfer devices also may require the use of apressure monitor to monitor the inflation pressure. Even when used inconjunction with a pressure monitor, it may not be able to achieve theproper inflation of the balloon.

The heat transfer device may be, for example, a pharyngeo-esophagealheat transfer device, an esophageal heat transfer device, anesophago-gastric heat transfer device, or a pharyngeo-esophago-gastricheat transfer device. For example, an esophageal heat transfer devicemay include a heat transfer region of about twenty (20) centimeters.Alternatively, an esophago-gastric heat transfer device may include aheat transfer region of about forty (40) centimeters. As yet anotheralternative, a pharyngeo-esophago-gastric heat transfer device mayinclude a heat transfer region of about forty-five (45) to about fifty(50) centimeters. Heat transfer devices of the present technology caninclude heat transfer regions of about 22, about 24, about 26, about 28,about 30, about 32, about 34, about 36, about 38, about 40, about 42,about 44, about 46, about 48, about 50, about 52, about 54, about 56,about 58, about 60, about 62, about 64 about 66, about 68 or about 70centimeters.

Heat transfer devices of the present technology can have a heat transferregion having a diameter of, for example, about 1.0 to about 2.0centimeters. The diameter of the heat transfer region can be about 1.1,about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about1.8, or about 1.9 centimeters. In certain embodiments, a heat transferregion of a heat transfer device of the present technology has a lengthof about 32 centimeters and a diameter of about 1.4 centimeters, givinga surface area of about 140 cm².

Increasing the length and/or circumference of the heat transfer regionof the device, and therefore the surface area of the heat transferregion, improves the speed and efficiency at which the patient is cooledor heated (or re-warmed). In certain embodiments the heat transferregion can be about 15 in², about 20 in², about 25 in², 30 in², about 35in², about 40 in², about 45 in², about 50 cm², about 60 cm², about 70cm², about 80 cm², about 90 cm², about 100 cm², about 110 cm², about 120cm², about 130 cm², about 140 cm², about 150 cm², about 160 cm², about170 cm², about 180 cm², about 190 cm², about 200 cm², about 210 cm²,about 220 cm², about 230 cm², about 240 cm², about 250 cm², about 260cm², about 270 cm², about 280 cm², about 290 cm², about 300 cm², about310 cm², about 320 cm², about 330 cm², about 340 cm², or about 350 cm².In certain embodiments, a heat transfer region can contact substantiallyall of the epithelial surface of a subject's esophagus.

The heat transfer device may be adapted to permit gastric access to thepatient's health care provider. The heat transfer device mayincorporate, for example, a gastric tube or gastric probe. The gastrictube or gastric probe may run parallel to the heat transfer mediumsupply tube and the heat transfer medium return tube. Alternatively, thegastric tube, the gastric probe, or both may be in a concentricarrangement with at least one of the heat transfer medium supply tube orthe heat transfer medium return tube. The gastric probe may be, forexample, a temperature probe.

The heat transfer device may incorporate, for example, multiple tubesand/or probes that, for example, permit access to the patient'sgastrointestinal system. The gastric tubes may be adapted to, forexample, deliver alimentation directly to a patient's stomach or to amore distal component of the gastrointestinal tract, such as thejejunum. The gastric tubes may also be adapted to, for example,administer medications to various components of the gastrointestinaltract, including esophageal mucosa, stomach, duodenum, and jejunum. Suchdevices allow for a relatively non-invasive method for controlling apatient's temperature while simultaneously administering alimentationand/or medication. Such methods and devices are superior to contemporarymethods to affect temperature control and modification, which do notreadily permit simultaneous medication and/or alimentationadministration and gastric decompression, despite the fact thatmedication administration through the gastrointestinal tract is in somecases of superior efficacy to intravenous administration. Thus, themethods and devices of the present technology allow for the provision ofalimentation and medication through the gastrointestinal tract, whilesimultaneously, allowing for temperature control and modification. Suchan approach is an improvement over intravenous administration ofnutrients and medications, adding substantially to the risk ofcomplications and the expense of treatment.

In certain embodiments, the heat transfer device may incorporate adevice that measures a physiological parameter such as temperature,pressure, oxygen saturation, pH, heart rate, Doppler signals,electromagnetic fluctuations, or chemical composition. For example, theheat transfer device may include or incorporate one or morethermometers, each with one or more temperature probes, for measuringthe ambient temperature, patient temperature, or heat transfer mediumtemperature. The thermometers may be separate devices or integrated withthe heat transfer system. Likewise, the heat transfer device may includeor incorporate electrochemical biosensors, or biologicalmicro-electromechanical systems (Bio-MEMS), allowing lab-on-chip (LOC)and incorporation of Micro Total Analysis Systems (pTAS) analysis ofbiochemical composition of the gastroesophageal environment. Inaddition, at least one aspect of the present technology provides one ormore methods for use of a lab-on-chip to perform biochemical assays,dielectrophoresis, real-time PCR, and immunoassays for the detection ofbacteria, viruses, and cancers.

In certain embodiments of the present technology, the heat transfersystem may further incorporate or include a device that measures aphysiological parameter such as pressure. For example, the heat transfersystem may include one or more sensors of esophageal pressure,transpulmonary pressure, and/or intra-abdominal pressure.

In certain embodiments of the present technology, the heat transferdevice comprises a pressure transducer located proximately, at any pointalong and throughout the midpoint, or distally, to allow measurement ofesophageal pressure and/or transpulmonary pressure. Direct measurementof esophageal pressure allows for a subsequent estimate oftranspulmonary pressure to provide, for example, guidance in supportinga patient with mechanical ventilation.

In patients with high pleural pressure on conventional ventilatorsettings, under-inflation may lead to atelectasis, hypoxemia, andexacerbation of lung injury. In patients with low pleural pressure,maintaining a low positive end-expiratory pressure (PEEP) keepstrans-pulmonary pressure low, avoiding over-distention and subsequentlung injury. Esophageal manometry has been used to identify the optimalventilator settings in order to avoid both under-inflation andover-inflation of the pulmonary system; however, the optimal level ofPEEP has been difficult to determine. Therefore, at least one aspect ofthe present technology provides one or more methods for measuringesophageal pressure as a means to estimate the transpulmonary pressureand subsequently determine optimal PEEP values that can maintainoxygenation of patients undergoing mechanical ventilation whilepreventing lung injury due to alveolar collapse or over-distention.

In certain embodiments of the present technology, the heat transferdevice comprises a pressure transducer located distally to allow directmeasurement of intra-abdominal pressure. The pressure transducer can beused to, for example, diagnose abdominal compartment syndrome. Abdominalcompartment syndrome is a complication of a wide variety of illnesses,including many of which are known or suspected to benefit from controlof a patient's temperature. For example, abdominal compartment syndromecan be a primary event developing from such conditions as pancreatitis,intraperitoneal hemorrhage from blunt trauma, penetrating trauma,perforation of an ulcer, or rupture of an aortic aneurysm. Abdominalcompartment syndrome can also develop as a secondary event after largeburns, sepsis, large volume resuscitation, penetrating or blunt trauma,or postoperatively.

At least one aspect of the present technology provides one or moremethods for measuring intra-abdominal compartment pressure anddiagnosing intra-abdominal compartment syndrome through theincorporation of a pressure transducer at the distal end of the device,which allows direct measurement of intra-abdominal pressure. The devicesand methods of the present technology provide for superior measurementof intra-abdominal pressure as compared to contemporary methods, such asthose mentioned in US Patent Application Publication 2009/0221933 toNagao et al., which are indirect, technically challenging, invasive, andtime-consuming.

Manufacture of heat transfer devices of the present technology can beaccomplished via stereolithography. Stereolithography is a manufacturingprocess in which parts are built one layer at a time using anultraviolet curable photopolymer resin, in a method referred to as anadditive manufacturing process.

Another embodiment of the present technology provides for a multi-lumenheat transfer device for inducing mild therapeutic hypothermia. The heattransfer device may include one or more lumens that provide a fluid pathfor circulation of a coolant. For example, the heat transfer device mayinclude a coolant supply tube and a coolant return tube. The lumens ofthe coolant supply tube and coolant return tube may be in fluidcommunication with each other thereby defining a fluid path for coolantflow. The coolant supply tube and coolant return tube may be arranged,for example, in parallel or concentrically.

Another embodiment of the present technology provides for a multi-lumenheat transfer device for controlling patient temperature. The heattransfer device may include one or more lumens that provide a fluid pathfor circulation of a heat transfer medium. For example, the heattransfer device may include a medium supply tube and a medium returntube. The lumens of the medium supply tube and medium return tube may bein fluid communication with each other thereby defining a fluid path formedium flow. The medium supply tube and medium return tube may bearranged, for example, in parallel or concentrically.

At least one aspect of the present technology provides a heat transferdevice comprising one or more lumens. For example, the device maycomprise a single lumen for delivery of a heat transfer medium to a heattransfer region of the device. As described herein, the heat transfermedium may be a gas (e.g., nitrous oxide, Freon, carbon dioxide, ornitrogen), liquid (e.g., water, saline, propylene glycol, ethyleneglycol, or mixtures thereof), solid (e.g., ice, metal, metal alloy, orcarbon fiber), slurry, and/or gel. In certain embodiments, the singlelumen may function as both the inflow lumen and the outflow lumen. Forexample, heat transfer medium may be delivered to the heat transferregion and extracted from the heat transfer region via the single lumenby, for example, an external pump that alternatively pumps and withdrawsheat transfer medium via the single lumen. In certain other embodiments,a solid heat transfer medium, which may comprise a heating element suchas a wire or coil; a thermoelectric module such as a Peltier module; ora carbon fiber such as a graphitic carbon fiber, may be inserted intothe single lumen.

In certain embodiments, the one or more lumens may be defined by a tubehaving a substantially helical configuration. The substantially helicalconfiguration of the tube creates an interior space defined by thehelix, which may comprise, for example, an access lumen. Thesubstantially helical tube can helically wrap around a separate probe ortube, such as a commercially available nasogastric or orogastric tube.In certain embodiments, such as esophageal heat transfer devices, thesubstantially helical configuration allows for gastric access. Forexample, the external walls of the tube having a substantially helicalconfiguration may define an access lumen. Where the heat transfer deviceis for placement within the esophagus, the tube having a substantiallyhelical configuration allows for gastric access via a gastric accesslumen. A separate probe, such as a temperature probe, or separate tube,such as a nasogastric tube or an orogastric tube, can be inserted intothe patient via the gastric access lumen. The separate probe or tube maybe inserted within the gastric access lumen before or after insertingthe device into the patient. Alternatively, the nasogastric ororogastric tube may be affixed (e.g., glued) to the substantiallyhelical tube. The nasogastric tube, orogastric tube, or probe may beprovided with the heat transfer device or provided as an after-marketcomponent.

In certain embodiments, the one or more lumens may be defined by a tubehaving a C-shaped cross section. In certain embodiments, such asesophageal heat transfer devices, the C-shaped design allows for gastricaccess. For example, the C-shaped design allows for the use of acommercially available probe, such as a temperature probe, or tube, suchas a nasogastric tube or an orogastric tube, with the heat transferdevice of the present technology. For example, the C-shaped tube canwrap around a commercially available nasogastric or orogastric tube. Thenasogastric or orogastric tube may be inserted within the interior spacedefined by the C-shaped tube before or after inserting the device intothe patient. Alternatively, the nasogastric or orogastric tube may beaffixed (e.g., glued) to the C-shaped tube.

Thus, in some embodiments, the present technology comprises anesophageal heat transfer system comprising an esophageal heat transferdevice and a nasogastric tube. In other embodiments, the presenttechnology comprises an esophageal heat transfer system comprising anesophageal heat transfer device and an orogastric tube. In still otherembodiments, the present technology comprises an esophageal heattransfer system comprising an esophageal heat transfer device and atemperature probe. In yet other embodiments, the present technologycomprises an esophageal heat transfer system comprising an esophagealheat transfer device and an orogastric tube, nasogastric tube, and/ortemperature probe.

Yet another embodiment of the present technology provides one or moredevices for cooling or warming multiple portions of a patient's bodysimultaneously. The devices comprise a heat transfer device including aproximal end, a distal end, at least one flexible tube extending betweenthe proximal and distal end, and additional flexible tubes extendingfrom the proximal end. The proximal end includes a heat transfer mediuminput port, a heat transfer medium output port, and about 2 to about 4ancillary tubes extending off the proximal end providing for additionalheat transfer medium flow pathways. The distal end of the device isconfigured for insertion into a larger orifice of a patient, while thedistal ends of the ancillary tubes are configured for insertion intoadditional smaller orifices or configured external as an externalcomponent for surface contact. For example, the ancillary tubes can beconfigured as a head and/or neck wrap to provide surface cooling.

At least one aspect of the present technology provides a heat transferdevice comprising (a) a plurality of lumens configured to provide afluid path for flow of a heat transfer medium; (b) a heat transferregion configured for contacting esophageal epithelium, nasopharyngealepithelium, auricular canal epithelium, and/or the tympanic membranes ofa patient; (c) a proximal end including an input port, an output port,and ancillary tubing containing heat transfer medium flow channels; and(d) a distal end configured for insertion into an esophagus of apatient. The heat transfer device can also comprise a hollow tube havinga distal end configured to extend into the patient's stomach. The heattransfer device can be capable of contacting substantially all of thepatient's esophageal epithelium, nasopharyngeal epithelium, auricularcanal epithelium, or the tympanic membranes.

Without wishing to be bound by theory, it is believed that affectingtemperature change through the nasopharynx and/or auricular canals hasthe benefit of affecting temperature change at a location in directproximity to the brain. The methods and devices of the presenttechnology overcome the logistical and technical challenges of affectingtemperature change through the nasopharynx and/or auricular canals.

A device for cooling or warming multiple portions of a patient's bodysimultaneously may be used to treat or prevent, for example, injurycaused by an ischemic condition; ischemia-reperfusion injury;neurological injury; or cardiac injury. The device may be used to treatpatients who have experienced or are experiencing myocardial infarction;stroke; traumatic brain injury; or ARDS. The methods of treating orpreventing such conditions or diseases comprise, for example, insertingthe distal end of the heat transfer device orally; advancing the distalend into the patient's esophagus; advancing the ancillary tubing intothe patient's nasopharynx and/or into the patient's auricular canals;initiating flow of a cooling medium along the fluid path; andcirculating the cooling medium along the fluid path for a timesufficient to induce systemic hypothermia in the patient. The patientmay be maintained in a state of hypothermia for at least two hours. Themethods may further comprise monitoring at least one physiologicalparameter of the patient, such as body temperature. The methods mayfurther comprise maintaining the patient's body temperature below about34° C.

The device may be used to control a patient's core body temperatureduring, for example, surgical procedures. The methods of controlling thepatient's core body temperature comprise, for example, inserting thedistal end of the heat transfer device nasally or orally; advancing thedistal end into the patient's esophagus; advancing the ancillary tubinginto the patient's nasopharynx and/or into the patient's auricularcanals; initiating flow of a cooling medium along the fluid path; andcirculating the heat transfer medium along the fluid path for a timesufficient to control core body temperature in the patient. The corebody temperature of the subject may be controlled for at least about twohours, for example. The methods may further comprise monitoring at leastone physiological parameter of the subject, such as body temperature.The methods may further comprise maintaining the patient's bodytemperature, for example, below about 34° C., between about 34° C. andabout 37° C., or at about 37° C.

Yet another embodiment of the present technology provides relativelynon-invasive devices and methods for heating or cooling a patient'sentire body while simultaneously maintaining a less drastic, or oppositedirection, local temperature change. Thus, at least one aspect of thepresent technology provides one or more methods for inducing systemichypothermia while simultaneously imparting local normothermia, forexample to the region of the esophagus in closest proximity to theatrium of the heart. Such methods and devices are superior tocontemporary methods to affect temperature control and modification,which can either warm or cool independently, but are unable to cool somesections of the body while simultaneously warming others, or vice versa.Because of differential effects of temperature change on organs andregions of the human body, the ability to impart varying degrees oftemperature differential, in similar or opposite directionssimultaneously at different parts of the body, is beneficial.

Certain embodiments of the present technology may utilize a controllersuch as that described in US20070203552 (Machold). For example, acontroller may employ a Peltier module to heat or cool a heat exchangeregion of the device, which would allow the device to alternate betweenheating and cooling modalities merely by changing the polarity of thecurrent flowing through the module. In addition, the amount of heat orcold generated can be adjusted by controlling the amount of currentflowing through the module. In particular, a controller may employ acascading proportional integrated differential (PID) control scheme. Insuch a scheme, a control system is provided that may be divided into twosections: (a) a Bulk PID control section which takes input from thehealth care provider or other user, such as target temperature, andinput from the sensors on the patient representing patient temperature,and calculates an intermediate set point temperature (SP1) and an outputsignal to the Heat Transfer Fluid PID control; and (b) the Heat TransferFluid PID control, that receives input from the Bulk PID control sectionand from a sensor representing the temperature of a heat transfer fluid,and generates a signal that controls the temperature of the heatexchanger by, for example, varying the power input to the heatexchanger.

The heat transfer fluid circulates in heat exchanger, so the HeatTransfer Fluid PID essentially controls the temperature of the heattransfer fluid. In this way, the control scheme is able to automaticallyachieve a specified target based on input from sensors placed on thepatient and the logic built into the controller. Additionally, thisscheme allows the unit to automatically alter the patient temperaturevery gradually the last few tenths of a degree to achieve the targettemperature very gently and avoid overshoot or dramatic, and potentiallydamaging, swings in the electronic power to the heat exchanger. Once thetarget temperature is achieved, the system continues to operateautomatically to add or remove heat at precisely the rate necessary tomaintain the patient at the target temperature.

In general, the controller can include a controlled variable, such aspump output, inflation/deflation pressure, or power input to the heatexchanger. A detecting unit or sensor can act as a feedback device fordetecting a parameter, such as patient temperature, intra-abdominalpressure, or the presence of air in a line, and outputting a feedbacksignal relative to the control variable. The control unit performs a PIDoperation, in which the controlled variable is adjusted according to thecomparison between the feedback signal and a predetermined target value.

As an example, the feedback signal T can represent patient temperatureand the predetermined target value T_(Targ) can represent a targettemperature set by a health care professional. When the feedback signalT is larger than the target value T_(Targ), it means that the patient'stemperature is too high. Accordingly, the controller, for example,increases or decreases pump output or power input to the heat exchangerin order to change the temperature and/or flow rate of the heat exchangemedium. When the feedback signal T is smaller than the target valueT_(Targ), it means that the patient's temperature is too low.Accordingly, the controller, for example, increases or decreases pumpoutput or power input to the heat exchanger in order to change thetemperature and/or flow rate of the heat exchange medium.

As another example, the feedback signal P can represent the patient'sintra-abdominal, esophageal, and/or gastric pressure and thepredetermined target value P_(Max) can represent a maximum pressure setby a health care professional. In certain embodiments, placement of anesophageal heat transfer device having an inflatable heat transferregion may cause elevated intra-abdominal, gastric, and/or esophagealpressure by preventing adequate gastric ventilation. When the feedbacksignal P approaches, reaches, and/or surpasses P_(Max), it means thatthe patient's intra-abdominal, esophageal, and/or gastric pressure is indanger of or has become unacceptably high. Accordingly, the controller,for example, decreases pump output or otherwise deflates the inflatableheat transfer region in order to allow for gastric ventilation.Following gastric ventilation, the feedback signal P should approach,reach, and/or fall below P_(Max) as the patient's intra-abdominal,esophageal, and/or gastric pressure is returning to or has returned toan acceptable level. Accordingly, the controller, for example, increasespump output or otherwise inflates the inflatable heat transfer region,thereby at least partially restricting gastric ventilation.

As yet another example, the controller may be programmed to periodicallyinflate and deflate the inflatable heat transfer region to prevent thebuild-up of intra-abdominal, esophageal, and/or gastric pressure. Forexample, the controller may increase pump output or otherwise inflatethe inflatable heat transfer region. The inflation time period may beabout 5 to about 60 minutes, including about 10, about 15, about 20,about 25, about 30, about 35, about 40, about 45, about 50, or about 55minutes. During this period of inflation, the subject may experienceelevated intra-abdominal, gastric, and/or esophageal pressure becauseadequate gastric ventilation is restricted by placement of theinflatable heat transfer region within the esophagus. Periodic deflationof the inflatable heat transfer region allows for adequate gastricventilation. For example, the controller may decrease pump output orotherwise deflate the inflatable heat transfer region. The deflationtime period may be about 1 to about 10 minutes, including about 2, about3, about 4, about 5, about 6, about 7, about 7, about 8, or about 9minutes.

Certain embodiments of the present technology provide an unexpectedlysuperior rate of temperature change relative to other devices andmethods. The present methods and devices can provide a rate of coolingof about 0.5° C./hour to about 2.2° C./hour in a large animal model ofsimilar size to an average adult human. Present methods and devices arecapable of demonstrating a total heat extraction capability of about 250kJ/hour to about 750 kJ/hour. For example, the present methods anddevices can provide a rate of cooling of about 1.2° C./hr to about 2.4°C./hr in a large animal model of similar size to an average adult human.Alternatively, the present methods and devices can provide a rate ofcooling of about 1.2° C./hour to about 1.8° C./hour in a large animalmodel of similar size to an average adult human, which demonstrates atotal heat extraction capability of about 350 kJ/hour to about 530kJ/hour. Methods and devices of the present technology can provide arate of cooling of about 1.3, about 1.4, about 1.5, about 1.6, and about1.7° C./hour. Methods and devices of the present technology are capableof demonstrating a total heat extraction capability of about 350, about360, about 370, about 380, about 390 about 400, about 410, about 420,about 430, about 440, about 450, about 460, about 470, about 480, about490, about 500, about 510, and about 520 kJ/hour.

While not wishing to be bound by any particular theory, it is thoughtthat the methods and devices of the present technology transfer moreheat per unit time than other devices. For example, heat transferdevices of the present technology include heat transfer regions that,for example, extend to substantially the entire length and/orcircumference of the patient's esophagus, providing increased contactsurface between the heat transfer region of the heat transfer device andpatient anatomy including, the esophageal epithelium and the vasculaturethat surrounds the esophagus. Heat transfer devices of the presenttechnology additionally enable reduction of gastric pressure throughgastric ventilation, thereby reducing the possibility of ballooning anddistention of the esophageal mucosa away from contact with theesophageal mucosa, and further enhancing heat transfer across theesophageal mucosa. In addition, materials for constructing the heattransfer devices of the present technology include those with superiorheat transfer characteristics. Heat transfer devices of the presenttechnology can be manufactured with thinner wall thicknesses, furtherreducing the heat transfer resistance across the device and increasingthe effectiveness of heat extraction from, or heat addition to, thepatient.

The presently described technology now will be described with respect tothe appended figures; however, the scope of the present technology isnot intended to be limited thereby. It is to be understood that thescope of the present technology is not to be limited to the specificembodiments described herein. The technology may be practiced other thanas particularly described and still be within the scope of the claims.

FIG. 1 is a schematic view of a heat transfer system 100 according to anembodiment of the present technology. The heat transfer system 100includes a heat transfer device 102, a heat exchanger 104, a heattransfer medium 106, and a network of tubular structures 108 forcirculating the heat transfer medium 106 between the heat transferdevice 102 and the heat exchanger 104.

The heat exchanger 104 is configured to heat or chill the heat transfermedium 106. The heat exchanger 104 may be any of a variety ofconventionally designed heat exchanger 104 s. For example the heatexchanger 104 may be a standard chiller, such as an RF-25 RecirculatingChiller manufactured by New Brunswick Scientific. The heat transfermedium 106 may be a gas, such as, for example, nitrous oxide, Freon,carbon dioxide, or nitrogen. Alternatively, the heat transfer medium 106may be a liquid, such as, for example, water, saline, propylene glycol,ethylene glycol, or mixtures thereof. In other embodiments, the heattransfer medium 106 may be a slurry, such as, for example, a mixture ofice and salt. In still other embodiments, the heat transfer medium 106may be a gel, such as, for example, a refrigerant gel. Alternatively,the heat transfer medium 106 may be a solid, such as, for example, iceor a heat conducting metal. For example, the heat transfer medium 106may comprise a heating element, such as a wire or ribbon. Such a wire orribbon may be straight or coiled and may comprise any metal orcombination of metals, including those that are routinely used such asiron-chromium-aluminum wires, nichrome wires, and copper-nickel wires.Alternatively, the heat transfer medium 106 may comprise a cooling tubecomprising a heat conducting metal. For example, the heat transfermedium 106 may comprise a copper tube. The copper tube may carry arefrigerant or blend comprising, for example, freon, hydrofluorocarbon,chlorofluorocarbon, or hydrochlorofluorocarbon. In yet anotherembodiment, a solid heat transfer medium 106 may comprise a carbonfiber, such as graphitic carbon fibers. In other embodiments, the heattransfer medium 106 may be formed, for example, by mixing a powder witha liquid. Thus, it should be understood that combinations and/ormixtures of the above-mentioned media may be employed to achieve a heattransfer medium 106 according to the present technology.

The network of tubular structures 108 for circulating the heat transfermedium 106 may include an external supply tube 110 and an externalreturn tube 112. The external supply tube 110 defines an external supplylumen 114 providing a fluid path for flow of the heat transfer medium106 from the heat exchanger 104 to the heat transfer device 102. Theexternal return tube 112 defines an external return lumen 116 providinga fluid path for flow of the heat transfer medium 106 from the heattransfer device 102 to the heat exchanger 104. A pump 118 may beemployed to circulate the heat transfer medium 106 through the networkof tubular structures 108, and the flow rate of the medium, and, hencethe heat transfer capabilities of the device, can be regulated byadjusting the pumping rate.

The heat transfer device 102 is adapted for placement within ananatomical structure of a mammalian patient. The heat transfer device102 has a proximal and a distal end. The distal end of the heat transferdevice 102 may be configured for insertion into a body orifice. Forexample, the distal end of the heat transfer device 102 may beconfigured for insertion into the nostrils, mouth, anus, or urethra of apatient. When properly inserted, the distal end of the heat transferdevice 102 may be ultimately positioned in the esophagus, rectum, colon,bladder, or other anatomical structure. The proximal end of the heattransfer device 102 includes an input port 120 and an output port 122.The input port 120 and output port 122 are connected to the network oftubular structures 108 for circulating the heat transfer medium 106. Forexample, the input port 120 may be connected to the external supply tube110 and the output port 122 may be connected to the external return tube112. Thus, in certain embodiments, the heat exchanger 104 may be influid communication with the heat transfer device 102 via the network oftubular structures 108.

In operation, the heat transfer device 102 is positioned into ananatomical structure, such as the esophagus. The heat exchanger 104 isused to heat or chill the heat transfer medium 106 that is supplied tothe heat transfer device 102 via the external supply tube 110. The heattransfer medium 106 flows through the external supply tube 110 andenters the heat transfer device 102 through the input port 120. The heattransfer medium 106 circulates through the heat transfer device 102 andexits the heat transfer device 102 through the output port 122, andreturns to the heat exchanger 104 via the external return tube 112.Raising or lowering the temperature of the heat transfer medium 106alters the body temperature of the patient.

The heat transfer system 100 may further incorporate a device thatmeasures a physiological parameter such as temperature, pressure, orelectromagnetic fluctuations. For example, the heat transfer system 100may include one or more thermometers 124, each with one or moretemperature probes 126, for measuring the ambient temperature, patienttemperature, or heat transfer medium 106 temperature. The thermometersmay be separate devices or integrated with the heat transfer system 100.

FIG. 2 depicts a heat transfer device 200 according to an embodiment ofthe present technology. For purposes of further elucidating thisembodiment, the heat exchanger will be referred to as a chiller (notshown) and the heat transfer medium will be referred to as a coolant.However, it should be understood that any suitable heat exchanger andany suitable heat transfer medium may be employed with the heat transferdevice depicted in FIG. 2.

The heat transfer device 200 comprises a distal end 202, a proximal end204, and a length of flexible tubing 206 extending therebetween. Theproximal end 202 includes an input port 208 for receiving coolant fromthe chiller and an output port 210 allowing coolant to return to thechiller.

The input port 208 comprises a standard plumbing tee fitting 212.Alternatively, any fitting with two or more open ends, such as a wyefitting may be employed. The fitting may be composed of any suitablematerial, including, for example metal, such as, copper or iron; metalalloy, such as steel or brass; or plastic, such as, polyvinyl chloride(“PVC”) or polyethylene (“PE”). A brass plug 214 is affixed to theproximal open end of the tee fitting 212. Alternatively, standard caps,such as metal or plastic caps, may be affixed to the proximal open endof the fitting. The plug 214 includes an opening to allow for tubingclearance. The plug 214 is affixed to the fitting with chemical sealant216, such as, for example, Room-Temperature Vulcanization (“RTV”)Silicone Sealant. In other embodiments, the input port 208 may bemanufactured in a way that eliminates the need for affixed end caps,such as, for example, by extrusion.

The output port 210 comprises a standard plumbing tee fitting 212.Alternatively, any fitting with two or more open ends, such as a wyefitting may be employed. The fitting may be composed of any suitablematerial, including, for example metal, such as, copper or iron; metalalloy, such as steel or brass; or plastic, such as, PVC or PE. Brassplugs 214 are affixed to the proximal open end and distal open end ofthe tee fitting. Alternatively, standard caps, such as metal, metalalloy, or plastic caps, may be affixed to the open ends of the fitting.Each plug 214 may include an opening to allow for tubing clearance. Theplugs 214 are affixed to the fitting with chemical sealant 216, such as,for example, RTV Silicone Sealant. In other embodiments, the output port210 may be manufactured in a way that eliminates the need for affixedend caps, such as, for example, by extrusion.

The length of tubing 206 extending between the proximal end 204 anddistal end 202 of the heat transfer device 200 is a coolant supply tube218. The coolant supply tube 218 may be composed of clear vinyl.Alternatively, the coolant supply tube 218 may be composed of othersuitable materials, such as, for example, flexible medical gradetransparent PVC. The dimensions of the coolant supply tube 218 may beapproximately 0.625″ outside diameter (“OD”)×0.500″ inside diameter(“ID”). The coolant supply tube 218 is affixed to the input port 208with chemical sealant 216, such as, for example, RTV Silicone Sealant.The coolant supply tube 218 extends from the input port 208 to thedistal end 202 of the heat transfer device 200. The length of thecoolant supply tube 218 may be about eighteen (18) to about fifty-two(52) centimeters. In certain embodiments, the length of the coolantsupply tube 218 may be from about eighteen (18) to about twenty-two (22)centimeters. In certain embodiments, the length of the coolant supplytube 218 may be from about thirty (30) to about forty-two (42)centimeters. In other embodiments, the length of the coolant supply tube218 may be from about forty-five (45) to about fifty-two (52)centimeters. The length of the coolant supply tube 218 can be aboutthirty-two (32) centimeters.

The distal end 202 of the heat transfer device 200 includes an end cap220. The end cap 220 may be composed of any suitable material,including, for example, metal, such as, copper or iron; metal alloy,such as steel or brass; or plastic, such as, PVC or PE. The end cap 220is affixed to the coolant supply tube with chemical sealant 216, suchas, for example, RTV Silicone Sealant.

A coolant return tube 222 may be positioned within the coolant supplytube 218. The coolant return tube 222 may be composed of clear vinyl.Alternatively, the coolant return tube 222 may be composed of othersuitable materials, such as, for example, flexible medical gradetransparent PVC. The outside diameter of the coolant return tube 222 issmaller than the inside diameter of the coolant supply tube 218. Forexample, the dimensions of the coolant return tube 222 may beapproximately 0.437″ outside diameter (“OD”)×0.312″ inside diameter(“ID”). The coolant return tube 222 may be affixed to one or both of theinput port 208 or output port 210 with chemical sealant 216, such as,for example, RTV Silicone Sealant.

The coolant return tube 222 does not extend to the end cap 220 at thedistal end 202 of the heat transfer device 200. Thus, the lumen of thecoolant supply tube 224 and the lumen of the coolant return tube 226 maybe in fluid communication with each other, thereby defining a fluid pathfor coolant flow.

In operation, the coolant enters the input port 208 and flows throughthe lumen of the coolant supply tube 224 to the distal end 202 of theheat transfer device 200, which may be positioned in, for example, theesophagus of a patient. The coolant then flows through the lumen of thecoolant return tube 226 to the output port 210. In operation, heat istransferred from, for example, the esophagus to the coolant, resultingin a decrease in the temperature of the esophagus, as well as adjacentorgans, and ultimately, systemic hypothermia.

In certain embodiments, additives with high heat transfer coefficient,such as copper, for example, may be added to the material used formanufacture of the coolant supply tube 218 or the coolant return tube222. In one embodiment, lengths of wire, for example, running linearlyor spiraling along the length of the tube may be included. In otherembodiments, particulate matter with a high heat transfer coefficientmay be mixed in to the material used for manufacture of the coolantsupply tube 218 or the coolant return tube 222 (for example, vinyl orPVC) before or during extrusion.

In certain embodiments, the walls of the coolant supply tube 218 and/orcoolant return tube 222 may be relatively thin. For example, the wall ofthe coolant supply tube 218 may be less than about 1 millimeter.Alternatively, the wall of the coolant supply tube 218 may be less thanabout 0.01 millimeter. In some embodiments, the wall of the coolantsupply tube 218 may be less than about 0.008 millimeters. As will beappreciated by one of skill in the art, the thickness of the walls ofthe heat transfer medium supply tube and/or heat transfer medium returntube may be modified in increments of about 0.001 millimeters, about0.01 millimeters, or about 0.1 millimeters, for example.

Optionally, the heat transfer device 200 may include a gastric tube 228,to allow for gastric access and, for example, gastric suctioning as wellas gastric lavage for diagnosis and/or therapeutic purposes, if sodesired. The gastric tube 228 may be composed of clear vinyl.Alternatively, the gastric tube 228 may be composed of other suitablematerials, such as, for example, flexible medical grade transparent PVC.The outside diameter of the gastric tube 228 is smaller than the insidediameter of the coolant return tube 222. For example, the dimensions ofthe gastric tube 228 may be approximately 0.250″ outside diameter(“OD”)×0.170″ inside diameter (“ID”). The gastric tube 228 may beaffixed to the most proximal port, either the input port 208 or theoutput port 210, with chemical sealant 216, such as, for example, RTVSilicone Sealant. The gastric tube 228 may allow the patient's healthcare provider to insert, for example, a nasogastric tube that allows forsuctioning of the gastric contents. Alternatively, the gastric tube 228may allow the patient's health care provider to insert, for example, agastric temperature probe (not shown).

Optionally, an antibiotic or antibacterial coating may be applied toportions of the coolant supply tube 218, the coolant return tube 222, orthe gastric tube 228. Particularly, an antibiotic or antibacterialcoating may be applied to portions of the tubes that, upon insertion toa patient, may contact, for example, a mucosal lining of the patient.For example, topical antibiotics, such as tobramycin, colistin,amphotericin B, or combinations thereof, may be applied to the tubes.Incorporation of an antibiotic or antibacterial coating may allowselective decontamination of the digestive tract (“SDD”), which mayfurther improve outcome.

As another alternative, all or part of the heat transfer device 200 canbe manufactured by, for example, extrusion. Employing such amanufacturing modality would eliminate the need to seal junctions oraffix end caps and reduce the points at which leaks may occur.

FIG. 3 depicts a heat transfer device 300 according to an embodiment ofthe present technology. The heat transfer device 300 comprises aproximal end 302, a distal end 306, and a length of flexible tubing 304extending therebetween.

All or part of the heat transfer device 300 can be manufactured by, forexample, extrusion. Employing such a manufacturing modality wouldeliminate the need to seal junctions or affix end caps and reduce thepoints at which leaks may occur. Alternatively, or additionally, a fastcuring adhesive, such as RTV silicone sealant or temperature-curablesealant can be used to seal junctions and/or bond tubing together. Theheat transfer device 300 can be constructed using a biocompatibleelastomer and/or plastic, and, optionally, adhesive. For example,biomedical grade extruded silicone rubber such as Dow Corning Q7 4765silicone, and an adhesive such as Nusil Med2-4213 can be used tomanufacture heat transfer device 300.

FIG. 3A shows a schematic view of the exterior of heat transfer device300. The heat transfer device 300 includes an input port 308, a heattransfer medium supply tube 310, a heat transfer medium return tube 312,and an output port 314. In one embodiment, the outer wall of the heattransfer medium supply tube 310 can be in direct contact with patienttissue upon placement of the heat transfer device 300 in a patient. Forexample, the outer wall of heat transfer medium supply tube 310 can bein direct contact with the patient's esophagus when the heat transferdevice 300 is inserted orally or nasally. The portion of the heattransfer medium supply tube 310 that can be in direct contact withpatient tissue can be part of the heat transfer region of the heattransfer device 300. Input port 308 is connected to the heat transfermedium supply tube 310 and allows for heat transfer medium to bedelivered to the lumen of the heat transfer medium supply tube 310.Input port 308 may be positioned along the length of the heat transfermedium supply tube 310, preferably proximal to the region of the heattransfer medium supply tube 310 that is capable of directly contactingthe patient tissue. Heat transfer medium may flow through the heattransfer medium supply tube 310 to the heat transfer medium return tube312. Output port 314 is connected to the heat transfer medium returntube 312 and may allow for heat transfer medium to exit the device.Output port 314 may be positioned along the length of the heat transfermedium return tube 312, preferably proximal to the heat transfer regionof heat transfer device 300. The heat transfer device also includes acentral tube 316 that, for example, allows for gastric access. Thecentral tube 316 is in a concentric arrangement with the heat transfermedium supply tube 310 or the heat transfer medium return tube 312 (seeFIG. 3B). The central tube lumen 318 provides the health careprofessional with access to, for example, the patient's stomach whilethe heat transfer device is positioned within the patient's esophagus.

FIG. 3C is a cross-sectional view along the line 3C, which is identifiedin FIG. 3B.

The outermost tube is the heat transfer medium supply tube 310. The heattransfer medium supply tube 310 extends from about the input port 308 toabout the distal end 306 of the heat transfer device 300. The length ofthe heat transfer medium supply tube 310 can be about eighteen (18) toabout seventy-five (75) centimeters. In a particular embodiment, thelength of the heat transfer medium supply tube 310 is about thirty-two(32) centimeters. The outside diameter of the heat transfer mediumsupply tube 310 can be, for example, about 1.0 to about 2.0 centimeters.In a particular embodiment, the outside diameter of the heat transfermedium supply tube 310 is about 1.4 centimeters.

Upon insertion into, for example, the esophagus of a patient, the wallof the heat transfer medium supply tube 310 can be in direct contactwith the patient's esophagus. As noted above, the length and/orcircumference of the heat transfer medium supply tube 310, and thereforethe surface area of heat transfer medium supply tube 310, can vary.Increasing the area of contact between the heat transfer device 300 andthe patient's esophagus improves the speed and efficiency at which thepatient is cooled or heated (or re-warmed). In certain embodiments thesurface area of the heat transfer medium supply tube 310 can be fromabout 50 cm² to about 350 cm². In a particular embodiment, the surfacearea of the heat transfer region of the heat transfer medium supply tube310 can be about 140 cm². In certain embodiments, the heat transfermedium supply tube 310 can contact substantially all of the epithelialsurface of a patient's esophagus.

Positioned within the heat transfer medium supply tube 310 is the heattransfer medium return tube 312. The outside diameter of the heattransfer medium return tube 312 is smaller than the inside diameter ofthe heat transfer medium supply tube 310. The heat transfer mediumreturn tube 312 does not extend to the distal end of the heat transfermedium supply tube 310. Thus, the heat transfer medium supply tube lumen320 and the heat transfer medium return tube lumen 322 are in fluidcommunication with each other, thereby defining a fluid path for theflow of the heat transfer medium.

Positioned within the heat transfer medium return tube is the centraltube 316. The outside diameter of the central tube 316 is smaller thanthe inside diameter of the heat transfer medium return tube 312. Thecentral tube 316 can be, for example, a gastric tube, to allow forgastric access. The central tube 316 can act as a gastric tube that, forexample, allows for suctioning of the gastric contents. The central tube316 also allows a health care professional to insert, for example, anasogastric tube that allows for suctioning of the gastric contents.Alternatively, the central tube 316 allows a health care professional toinsert, for example, a gastric temperature probe.

The distal end of the heat transfer medium supply tube 310 can be sealedwith an end cap 324. The end cap 324 can be constructed from, forexample, silicone. The end cap 324 can include a hole or otherpassageway through which central tube 316 can pass. Likewise, theproximal end of the heat transfer medium return tube 312 can be sealedwith an end cap 326. The end cap 326 can be constructed from, forexample, silicone. The end cap 326 can include a hole or otherpassageway through which central tube 316 can pass. Junctions betweenthe various components and tubes can be sealed with a sealant 328, suchas Nusil Med2-4213.

FIG. 4 shows several views of a proximal end of a heat transfer deviceaccording to the present technology.

The heat transfer device comprises at least two concentrically arrangedtubes, such as a heat transfer supply tube 402 and a heat transferreturn tube 404, forming a multi-lumen heat transfer device having agenerally coaxial lumen configuration. The proximal ends of each of theheat transfer supply tube 402 and the heat transfer return tube 404 canbe sealed with end caps (not shown). The heat transfer device,optionally, includes a first central tube 410 and/or a second centraltube 412. For example, the heat transfer device can comprise one or moregastric tubes.

The heat transfer supply tube lumen 406 is of sufficient diameter toallow passage of the heat transfer return tube 404. Likewise, the heattransfer return tube lumen 408 may be of sufficient diameter to allowpassage of the first central tube 410 and/or the second central tube412. The first central tube 410 and the second central tube 412 can be,for example gastric tubes that provide access to the patient's stomachand allow for suctioning of gastric contents and/or placement of agastric temperature probe. The end cap (not shown) of the heat transferreturn tube 404 can include a hole or other passageway through whichcentral tubes 410 and 412 pass.

The heat transfer supply tube 402 may be coupled to an input port 414.Preferably, input port 414 is in a position such that upon insertion ofthe device, input port 414 remains external to the patient. The inputport 414 may be coupled to an external supply tube (not shown) equippedwith standard connectors for interface with a chiller and/or warmingdevice. The heat transfer return tube 404 may be coupled to an outputport 416. Preferably, output port 416 is in a position such that uponinsertion of the device, output port 416 remains external to thepatient. The output port 416 may be coupled to an external return tube(not shown) equipped with standard connectors for interface with thechiller and/or warming device.

FIG. 5 shows schematic and cross-section views of a distal end of a heattransfer device according to the present technology.

The heat transfer device as depicted in FIG. 5A comprises at least twoconcentrically arranged tubes, such as a heat transfer supply tube 502and a heat transfer return tube 504, to form a multi-lumen heat transferdevice having a generally coaxial lumen configuration. The distal end ofthe heat transfer supply tube 502 extends beyond the distal end of heattransfer return tube 504 such that the heat transfer supply tube 502 andheat transfer return tube 504 form a heat transfer flow path. The distalend of the heat transfer supply tube 502 can be rounded or otherwiseformed to facilitate insertion and positioning of the heat transferdevice in the patient's esophagus. The heat transfer device can alsocomprise a first central tube 506 and/or a second central tube 508. Thefirst central tube 506 and the second central tube 508 can be, forexample gastric tubes that provide access to the patient's stomach andallow for suctioning of gastric contents and/or placement of a gastrictemperature probe.

FIG. 5B is a cross-sectional view along the line 58, which is identifiedin FIG. 5A. The heat transfer supply tube 502 and the heat transferreturn tube 504 are arranged concentrically. The heat transfer returntube 504 is positioned within the heat transfer supply tube lumen 510.The first central tube 506 and the second central tube 508 arepositioned within the heat transfer return tube lumen 512. A health careprofessional can, for example, insert a gastric temperature probe (notshown) through the first central tube lumen 514 and/or the secondcentral tube lumen 516.

FIGS. 5B-5Q depict additional arrangements of the tubes and lumens thatcomprise exemplary heat transfer devices and systems of the presenttechnology. FIGS. 5B-5Q show cross-sectional (FIGS. 5B-5I), andcorresponding schematic (5J-5Q), views of several alternativeconfigurations of multi-lumen and single-lumen heat transfer devicesand/or systems according to embodiments of the present technology.

As shown in FIG. 5C and corresponding FIG. 5K, the heat transfer supplytube lumen 510 and the heat transfer return tube lumen 512 can bearranged in parallel to each other. As shown in FIG. 5D andcorresponding FIG. 5L, the first central tube lumen 514 and the secondcentral tube lumen 516 can also be arranged in parallel to the heattransfer supply tube lumen 510 and the heat transfer return tube lumen512. Alternatively and as shown in FIGS. 5E and 5F, and correspondingFIGS. 5M and 5N, the first central tube lumen 514 and/or the secondcentral tube lumen 516 can be positioned between the heat transfersupply tube lumen 510 and the heat transfer return tube lumen 512. Inyet another alternative and as shown in FIG. 5G and corresponding FIG.50, the first central tube lumen 514 can abut and run in parallel to theheat transfer supply tube 502 and/or the heat transfer return tube 504.Optionally, a gastric tube or a gastric probe can be inserted into apatient's stomach via the first central tube lumen 514 and/or the secondcentral tube lumen 516. In some embodiments, a commercially availabletube, such as a nasogastric tube or an orogastric tube, can be insertedinto the patient's stomach via the first central tube lumen 514 and/orthe second central tube lumen 516. Such tubes are well known to those ofskill in the art. In certain embodiments, the first central tube 506and/or the second central tube 508 serve as a gastric tube and the needto place a separate nasogastric or orogastric tube is eliminated.

As shown in FIG. 5H and corresponding FIG. 5P, heat transfer supply tube502 defining the heat transfer supply tube lumen 510 and the heattransfer return tube 504 defining the heat transfer return tube lumen512 can be arranged to form a C-shape, defining a central interior 518.In embodiments such as an esophageal heat transfer device, the C-shapeddesign can allow for gastric access. For example, the C-shaped designallows for the use of a commercially available probe, such as atemperature probe, or tube, such as a nasogastric tube or an orogastrictube, with the heat transfer device. The nasogastric tube, orogastrictube, or probe (not shown) may be placed within the central interior 518of the C-shape formed by the heat transfer supply tube 502 and the heattransfer return tube 504. The nasogastric tube, orogastric tube, orprobe (not shown) may be provided with the heat transfer device orprovided as an after-market component.

As shown in FIG. 5I and corresponding FIG. 5Q, a heat transfer devicemay comprise a single heat transfer lumen 520 defined by heat transfertube 522. The single heat transfer lumen 520 may serve as the heattransfer supply tube lumen 510 and the heat transfer return tube lumen512. For example, heat transfer medium may be delivered to a heattransfer region of the device and extracted from the heat transferregion via the single heat transfer lumen 520 by, for example, anexternal pump (not shown) that alternatively pumps and withdraws heattransfer medium via the single lumen. In certain other embodiments, asolid heat transfer medium, which may comprise a heating element such asa wire or coil; a thermoelectric module such as a Peltier module; or acarbon fiber such as a graphitic carbon fiber, may be inserted into thesingle heat transfer lumen 520. Optionally, at least one central tube506 defining at least one central lumen 514 can abut and run in parallelto heat transfer tube 522. The central tube 506 can be, for example agastric tube that provides access to the patient's stomach and allowsfor suctioning of gastric contents and/or placement of a gastrictemperature probe. A gastric tube, such as a nasogastric or orogastrictube, or a gastric probe can be inserted into a patient's stomach viathe central tube lumen 514. Alternatively, the central tube 506 canserve as a gastric tube and the need to place a separate nasogastric ororogastric tube is eliminated.

The esophageal heat transfer device shown in FIGS. 2-5 and furtherdiscussed herein above is merely exemplary and not meant to be limitingto the present technology. The heat transfer device of the presenttechnology may be configured for insertion into the ears, nostrils,mouth, anus, or urethra of a patient. When properly inserted, the heattransfer portion of the device may be ultimately positioned in theauricular canal, nasopharynx, esophagus, stomach, rectum, colon,bladder, or other anatomical structure.

FIG. 6 depicts a cross-sectional and longitudinal view of heat transferdevice 600 according to an embodiment of the present technology.

FIG. 6A depicts a longitudinal view of heat transfer device 600according to an embodiment of the present technology. The heat transferdevice 600 comprises a proximal end 602 and a distal end 604. The heattransfer device 600 includes an inlet port 606, a heat transfer mediumsupply tube 608, a heat transfer medium return tube 610, and an outletport 612. The distal end of the heat transfer medium supply tube 608extends beyond the distal end of heat transfer medium return tube 610such that the heat transfer medium supply tube 608 and heat transfermedium return tube 610 form a heat transfer medium flow path. The heattransfer device also includes a central tube 614 that, for example,allows for gastric access. The central tube 614 is in a concentricarrangement with the heat transfer medium supply tube 608 or the heattransfer medium return tube 610 or both, to form a multi-lumen heattransfer device having a generally coaxial lumen configuration. Thecentral tube 614 can be, for example, a gastric tube that providesaccess to the patient's stomach and allows for suctioning of gastriccontents and/or placement of a gastric temperature probe. The centraltube lumen 616 provides the health care professional with access to, forexample, the patient's stomach while the heat transfer device ispositioned within the patient's esophagus.

FIG. 6B depicts a cross-sectional view of heat transfer device 600according to an embodiment of the present technology. The heat transfermedium supply tube 608 and the heat transfer medium return tube 610 arearranged concentrically. The heat transfer medium return tube 610 ispositioned within the inflow channel 618, which is defined by heattransfer medium supply tube 608. The central tube 614 is positionedwithin outflow channel 620, which is defined by heat transfer mediumreturn tube 610. A health care professional can, for example, insert agastric temperature probe (not shown) through the central tube lumen616. The heat transfer medium supply tube 608 and the heat transfermedium return tube 610 have inner surfaces comprised of a plurality ofsplines 622. The plurality of splines 622 surround the heat transfermedium flow path, thereby helping to enhance the likelihood ofmaintenance of laminar flow, and reduce the likelihood of flowobstruction.

FIG. 7 depicts a schematic view of a distal end of a heat transferdevice according to an embodiment of the present technology.

In certain embodiments, an esophageal heat transfer device incorporatesa gastric tube 702. The gastric tube 702 may be the center tube of theconcentric arrangement of tubes and may comprise a generally hollow tubethat provides gastric access. For example, a tube that allows forsuctioning of the gastric contents may be inserted into the patient'sstomach via the gastric tube 702. In certain embodiments a commerciallyavailable tube, such as a nasogastric tube or an orogastric tube, can beinserted into the patient's stomach via the gastric tube 702. Such tubesare well known to those of skill in the art. In certain embodiments, thegastric tube 702 serves as a tube for suctioning stomach contents andthe need to place a separate nasogastric tube is eliminated. As anotherexample, a gastric temperature probe may be inserted via the gastrictube 702.

The gastric tube 702 may include several ports 704 that serve as smalltubular connections or passageways from the external environment (here,the patient's stomach) to gastric tube lumen 706. The ports 704 maycommunicate directly (and only) with the gastric tube lumen 706. Theports 704 may be positioned at the distal end of the heat transferdevice to provide additional communication portals between the patient'sstomach and the gastric tube 702. The ports 704 provide for additionalpassageways for gastric contents to flow from the patient's stomach outthrough the gastric tube lumen 706, thereby reducing the likelihood ofblockage of the single lumen from semi-solid stomach contents.

In other embodiments, an esophago-gastric heat transfer device comprisesconcentric tubes such that the center-most tube serves as a gastric tube702. In such an arrangement, the outermost tube can be, for example, aheat transfer medium supply tube 708. A heat transfer medium return tube710 can be positioned within the heat transfer medium supply tube 708.Likewise, the gastric tube 702 can be positioned within the heattransfer medium return tube 710.

As shown in FIG. 7, the heat transfer device may be an esophageal oresophago-gastric heat transfer device and comprise three concentricallyarranged tubes, including a heat transfer medium supply tube 708, a heattransfer medium return tube 710, and a gastric tube 702 to form amulti-lumen heat transfer device having a generally coaxial lumenconfiguration. The heat transfer portion of the heat transfer device maybe confined to the patient's esophagus, while the gastric tube 702extends into the patient's stomach. The heat transfer device may furtherinclude ports 704 along the side of the gastric tube 702. The distal endof the gastric tube 702 includes several ports along the side of thetube to provide access to the gastric tube lumen 706, thereby reducingthe likelihood of blockage of the single lumen from semi-solid stomachcontents. The addition of such ports 704 may improve and enhance theremoval of stomach contents, which, in turn, may improve contact betweengastric mucosa and the heat transfer device. Such improved contact mayenhance heat transfer between the heat transfer device and the gastricmucosa.

The configuration of the ports as shown in FIG. 7 is oval. However, theports can be, for example, circular, rectangular, or any other shapethat permits flow of gastric contents from the stomach to the gastrictube lumen 706.

FIG. 8 depicts a heat transfer device 800 according to an embodiment ofthe present technology. The heat transfer device 800 comprises aproximal end 802, a distal end 806, and a length of flexible tubing 804extending therebetween. The length of flexible tubing 804 may comprise aheat transfer region. The distal end 806 of the heat transfer device 800may be configured for insertion into a body orifice. For example, thedistal end 806 of the heat transfer device 800 may be configured forinsertion into the nostrils or mouth of a patient. When properlyinserted, the heat transfer region of the heat transfer device 800 maybe ultimately positioned in the esophagus, or other anatomicalstructure. Upon placement in, for example, the esophagus of a patient,the heat transfer region of the heat transfer device 800 can be indirect contact with the patient's esophagus. In certain embodiments, theheat transfer region of the heat transfer device 800 can contactsubstantially all of the epithelial surface of a patient's esophagus.The distal end 806 of the heat transfer device 800 may be configured toextend into a stomach of a patient.

All or part of the heat transfer device 800 can be manufactured by, forexample, extrusion. Employing such a manufacturing modality wouldeliminate the need to seal junctions or affix end caps and reduce thepoints at which leaks may occur. Alternatively, or additionally, a fastcuring adhesive, such as RTV silicone sealant or temperature-curablesealant can be used to seal junctions and/or bond tubing together. Theheat transfer device 800 can be constructed using a biocompatibleelastomer and/or plastic, and, optionally, adhesive. For example,biomedical grade extruded silicone rubber such as silicone rubberavailable from Dow Corning (e.g., Q7-4765, C6-165, and/or C6-550), andan adhesive such as Nusil Med2-4213 can be used to manufacture heattransfer device 800.

FIG. 8A shows a schematic view of the exterior of heat transfer device800. The heat transfer device 800 includes an input port 808 and anoutput port 810. The heat transfer device 800 includes a gastric tube812 that, for example, allows for gastric access. The proximal end ofthe gastric tube can be adapted to accommodate attachment to, forexample, a suctioning device.

FIG. 8C is a cross-sectional view of the heat transfer device 800. Theheat transfer device 800 comprises an internal cavity 816 and a gastrictube 812. The gastric tube 812 defines a gastric lumen 818. As shown inFIGS. 8B and 8C, the distal end 806 of the heat transfer device 800includes one or more ports 814 along the side of the gastric tube 812.The ports 814 may provide for communication between the space exteriorto the device 800 and the gastric tube lumen 818. For example, the ports814 may act as a portal between the patient's stomach and the gastrictube lumen 818 allowing the gastric contents to be suctioned from thepatient's stomach out through the gastric tube lumen 818. The presenceof multiple ports 814 provides reduced likelihood of blockage of thegastric tube lumen 818 from semi-solid stomach contents. Alternatively,multiple gastric tube lumens may be employed. The addition of ports 814may improve and enhance the removal of stomach contents, which, in turn,may improve contact between gastric mucosa and the heat transfer device800. Such improved contact may enhance heat transfer between the heattransfer device 800 and the gastric mucosa. The configuration of theports 814 shown in FIG. 8 is oval. However, the ports 814 can be, forexample, circular, rectangular, or any other shape that permits flow ofgastric contents from the stomach to the gastric tube lumen 818.

FIG. 8D is a cross-sectional view of the heat transfer device 800 alongthe line D-D shown in FIG. 8A. The internal cavity 816 can be divided bywall 820 into a multi-lumen cavity comprising, for example, a heattransfer medium supply lumen 822 and a heat transfer medium return lumen824. The heat transfer medium supply tube lumen 822 and the heattransfer medium return tube lumen 824 may be in fluid communication witheach other, thereby defining a fluid path for the flow of the heattransfer medium.

The gastric lumen 818 is in a concentric arrangement with the interiorcavity 816. As discussed above, the gastric tube lumen 818 provides thehealth care professional with access to, for example, the patient'sstomach while the heat transfer device 800 is positioned within thepatient's esophagus.

FIGS. 9A-9D depict schematic representations of a portion of anexemplary heat transfer device according to the present technology. Theportion of the heat transfer device represents all or part of a heattransfer region 900. The heat transfer region 900 comprises a tube 902having a substantially helical configuration. The tube 902 defines aninternal lumen 904, which is capable of receiving a heat transfermedium. For example, the internal lumen 904 may provide a fluid path forthe flow of a liquid or gaseous heat transfer medium. In one embodiment,the tube 902 may serve as the evaporative component of a freon/gascircuit and be connected with an external condenser (not shown).Alternatively, the internal lumen 904 may be capable of receiving asolid or semi-solid heat transfer medium.

The substantially helical configuration of the tube 902 creates aninterior space 906 defined by the helix, which serves as, for example,an access lumen. The access lumen allows for access to anatomical sitesbeyond the placement of the heat transfer device. For example, where theheat transfer device is for placement within the esophagus, the helicalarrangement allows for gastric access via the interior space 906, whichserves as, for example, a gastric access lumen. The helical designallows for the use of a commercially available probe, such as atemperature probe, or tube, such as a nasogastric tube or an orogastrictube, with the heat transfer device. The nasogastric tube, orogastrictube, or probe (not shown) may be placed within the interior 906. Thenasogastric tube, orogastric tube, or probe (not shown) may be providedwith the heat transfer device or provided as an after-market component.

In certain embodiments, the term “patient” refers to a mammal in need oftherapy for a condition, disease, or disorder or the symptoms associatedtherewith. The term “patient” includes dogs, cats, pigs, cows, sheep,goats, horses, rats, mice and humans. The term “patient” does notexclude an individual that is normal in all respects.

As used herein, the term “treating” refers to abrogating; preventing;substantially inhibiting, slowing or reversing the progression of;substantially ameliorating clinical and/or non-clinical symptoms of; orsubstantially preventing or delaying the appearance of clinical and/ornon-clinical symptoms of a disease, disorder or condition.

In the preceding paragraphs, use of the singular may include the pluralexcept where specifically indicated. As used herein, the words “a,”“an,” and “the” mean “one or more,” unless otherwise specified. Inaddition, where aspects of the present technology are described withreference to lists of alternatives, the technology includes anyindividual member or subgroup of the list of alternatives and anycombinations of one or more thereof.

The disclosures of all patents and publications, including publishedpatent applications, are hereby incorporated by reference in theirentireties to the same extent as if each patent and publication werespecifically and individually incorporated by reference.

It is to be understood that the scope of the present technology is notto be limited to the specific embodiments described above. The presenttechnology may be practiced other than as particularly described andstill be within the scope of the accompanying claims.

Likewise, the following examples are presented in order to more fullyillustrate the present technology. They should in no way be construed,however, as limiting the broad scope of the technology disclosed herein.

EXAMPLES Example 1 Cooling of a Model System

An experiment was conducted to quantify the approximate rate oftemperature reduction achievable by use of an exemplary embodiment ofthe present technology. Target temperature reduction is 4° C. Data werecollected and plotted on a common X-Y graph, as shown in FIG. 10.

The arrangement of equipment for this experiment is shown in FIG. 1. Abrief description of each piece of equipment is as follows:

-   -   1. The heat transfer device 102 was an exemplary embodiment of a        heat transfer device according to the present technology    -   2. An insulated container, 96 cm (l)×36 cm (w)×36 cm (h),        containing 88 kg water at the initial temperature shown in Table        1 represented the mass to be cooled.    -   3. A 110V electric pump, Little Giant Model PES-70 (4.4 L/min        free-flow) was used to circulate hot water within the insulated        container (2) to maintain homogeneous temperature of water        within this container.    -   4. The heat exchanger 104 comprised an insulated container, 51        cm (l)×28 cm (w)×34 cm (d), containing 40 kg ice water.    -   5. The pump 118 comprised a 110V electric pump, Little Giant        Model PES-70 (250 mL/min as installed) and was used to provide        circulation of coolant from the heat exchanger 104 through the        external supply tube 110, then through the heat transfer device        102, then through the external return tube 112, and back to the        heat exchanger 104.    -   6. The external supply tube 110 comprised a Watts clear vinyl        #SVKI10, ⅝″ (od)×½″ (id)×42″ (l), to carry coolant from the heat        exchanger 104 to the heat transfer device 102.    -   7. The external return tube 112 comprised a Watts clear vinyl        #SVKI10, ⅝″ (od)×½″ (id)×42″ (l), to carry coolant from heat        transfer device 102 to the heat exchanger 104.    -   8. A thermometer 124, such as a digital waterproof thermometer        including 2 remote probes 126, Taylor Model 1441, was used to        monitor:        -   a. coolant temperature (T₃ as shown in FIG. 1) near the            discharge of the external return tube 112 into the heat            exchanger 104;        -   b. ambient temperature (T₄ as shown in FIG. 1) within test            cell.    -   9. A thermometer 124, such as a digital waterproof thermometer        including 2 remote probes 126, Taylor Model 1441, was used to        monitor:        -   a. hot water temperature (T₁ as shown in FIG. 1) within            insulated container (2), at the end opposite circulation            pump (3).        -   b. hot water temperature (T₂ as shown in FIG. 1) within            insulated container (2), at the end nearest circulation pump            (3).

The body to be cooled in each iteration of this experiment was an 88-kgmass of water, which was held in an insulated container (2) measuring94×36×26 cm. This mass was chosen as it is representative of the bodymass of a typical adult male. Heat transfer to ambient air by freeconvection was through the 94×36 cm top surface of the body of water.Initial temperature of this mass of water for each iteration of theprocedure is shown in Table 1.

The coolant for each iteration of this experiment was a 30-kg mass ofwater containing an additional 10-kg of ice, which was held in aninsulated container. Ice was used to keep the temperature of the coolantnearly constant for the duration of each iteration of the experimentwithout the need for a powered chiller, and was replenished at the startof each iteration for which the conductive cooling mode was enabled.

There are two modes of temperature reduction to consider in thisexperiment. They are convective cooling to ambient air, and conductivecooling through the heat transfer device. To quantify the contributionof each mode to the total temperature reduction, a control case was runwith the conductive cooling mode disabled (no coolant circulated throughthe heat transfer device). The procedure was then run two additionaltimes with the conductive cooling mode enabled (the heat transfer devicewas submerged in the body of hot water, and coolant circulated throughit). The difference between temperature reduction rates, with andwithout conductive cooling enabled, is the temperature reduction ratedue to conductive cooling through the heat transfer device.

Summary of data for each iteration of the experiment is shown in Table 1below:

TABLE 1 Cooling Experiment Results 4° C. T_(init,avg) T_(amb,avg)T_(coolant,avg) drop time Iteration Description ° C. ° C. ° C. (hh:mm) 1Control case, 38.8 19.6 N/A 02:53 convection to ambient only 2Conductive cooling 39.4 20.3 3.9 01:39 enabled, Run #1 3 Conductivecooling 38.1 20.4 3.5 01:38 enabled, Run #2 In Table 1: “T_(init,avg)”is the average initial temperature of the body to be cooled, average oftwo readings “T_(amb,avg)” is the average ambient temperature for theduration of the iteration “T_(coolant,avg)” is the average coolanttemperature for the duration of the iteration “4° C. drop time” is thetime required to achieve a 4° C. reduction in average temperature of thebody to be cooled.

Thus, conductive cooling through the exemplary heat transfer deviceemployed in this Example significantly decreases time to achieve a 4° C.temperature reduction.

Example 2 Operative Temperature Management

A heat transfer device according to the present technology was utilizedin an animal study as described below. The heat transfer region of theheat transfer device was approximately 70 centimeters in length (toaccommodate the length of the snout) and had a diameter of about 1.4centimeters, for a surface area of about 305 cm².

A large swine with a mass of 70 kg was chosen to best represent the sizeand average mass of a human patient. The swine was singly housed in anAssociation for the Assessment and Accreditation of Laboratory AnimalCare, International (AAALAC) accredited facility, with primaryenclosures as specified in the USDA Animal Welfare Act (9 CFR Parts 1, 2and 3) and as described in the Guide for the Care and Use of LaboratoryAnimals (National Academy Press, Washington D.C., 1996).

The swine was anesthetized with a pre-anesthetic mix ofTelozole/Xylazine, then provided with anesthesia via inhalational routewith isoflurane 2% after endotracheal intubation achieved with standardendotracheal intubation equipment and technique well known to thoseskilled in the art. Muscular paralysis was obtained with intravenousparalytic. Temperature was monitored continuously via rectalthermocouple probe placed after anesthesia and endotracheal intubation.

A commercially available thermal water bath and circulator (GaymarMeditherm MTA-5900) was utilized to provide a controlled-temperatureheat transfer medium to the heat transfer device. The specific heattransfer medium utilized was distilled water. Specifications of thecommercially available thermal water bath and circulator are as follows:

Dimensions: 94 cm H×35 cm W×48 cm D

Weight: 54.9 kg empty; 64.0 kg full

Material: Aluminum Shell, 16 Gauge Steel Chassis

Flow Rate: 1 liter per minute

Power: 220V, 240V, 50 Hz, 6 A

Temperature: Manual: 4 to 42° C., Automatic: 30 to 39° C.

Electrical Cord: 4.6 m detachable power cord

The heat transfer device was connected to the thermal water bath andcirculator, which was then powered on and allowed to equilibrate whilepreparing the swine.

After successful anesthesia, paralysis, and endotracheal intubation ofthe swine, a central semi-rigid stylet was placed into the heat transferdevice and the heat transfer device was lubricated with a biocompatiblelubricant.

The heat transfer device was then introduced into the esophagus of theswine using standard esophageal intubation technique well known to thoseskilled in the art. An external measurement of the distance fromoropharyngeal opening to xiphoid process served as an indicator to whichthe depth of the heat transfer device was inserted. Confirmation ofproper depth of insertion was obtained by successful aspiration ofgastric contents through the gastric lumen of the heat transfer device.

In order to demonstrate the capacity of the heat transfer device tosuccessfully warm a patient under hypothermic conditions typically foundin the operating room environment, the swine was cooled by setting thesupply temperature of the heat transfer medium to the low set point (4°C.) for a time sufficient to reduce the temperature of the swine to33.6° C.

Data from the cooling portion of the experiment are shown in Table 2. Ascan be seen in Table 2, a 1° C. reduction in core body temperature of a67.5 kg swine was achieved in about 40 minutes; a 2° C. reduction incore body temperature of a 67.5 kg swine was achieved in about 80minutes; a 3° C. reduction in core body temperature of a 67.5 kg swinewas achieved in about 125 minutes; and a 4° C. reduction in core bodytemperature of a 67.5 kg swine was achieved in about 175 minutes.

TABLE 2 Esophageal Cooling. Time (min) Rectal Temperature (° C.) 0 37.810 37.8 15 37.6 20 37.4 25 37.3 32 37.2 35 37 40 36.8 45 36.7 50 36.6 5536.4 60 36.3 65 36.1 70 36 75 35.9 80 35.7 85 35.6 90 35.5 95 35.4 10035.3 105 35.2 110 35.1 115 35 120 34.9 125 34.8 130 34.7 135 34.6 14034.5 145 34.4 150 34.4 155 34.3 160 34.2 165 34.1 170 33.9 175 33.8 18033.7 185 33.6

FIG. 11 shows a comparison of the rate of cooling achieved by a heattransfer device of the present technology as compared to the rate ofcooling demonstrated in US Patent Application Publication 2004/0210281to Dzeng et al. (now U.S. Pat. No. 7,758,623). In order to make anaccurate comparison, and to properly account for the differences in massbetween the two experiments, the total amount of heat extracted in eachcase is calculated in standard units of Joules. Using a standardspecific heat capacity of water (c_(p)=4.186 J/g C) to model thespecific heat capacity of the experimental animal, the heat extracted ateach time point is calculated as Q=m(ΔT)c_(p), where m is the mass ofthe experimental animal, and ΔT is the temperature difference obtainedat each time point.

At the time point of one hour, the total heat extracted is 439 kJ in onehour (122 Watts) with a heat transfer device of the present technology,as compared to a total heat extraction of 260 kJ in one hour (72 Watts)achieved with the device mentioned by Dzeng et al. in US PatentApplication Publication 2004/0210281 (now U.S. Pat. No. 7,758,623).

The results of the swine cooling experiment show that even in arelatively large animal, with correspondingly greater heat reservoircapacity, a significantly greater heat transfer rate is achievable witha heat transfer device of the present technology than with prior devicessuch as those mentioned by Dzeng et al. in US Patent ApplicationPublication 2004/0210281 (now U.S. Pat. No. 7,758,623). From the datapresented, the total heat extracted, and the consequent coolingachieved, can be seen to be significantly greater with a heat transferdevice of the present technology as compared to the rate of heattransfer and cooling achieved with prior devices such as those mentionedby Dzeng et al. in US Patent Application Publication 2004/0210281 (nowU.S. Pat. No. 7,758,623). Thus, it was unexpectedly and surprisinglyobserved that the cooling rate achieved with a heat transfer device ofthe present technology is significantly greater than that achieved withother devices and that the methods and devices of the present technologytransfer more heat per unit time than other devices. Without wishing tobe bound by any particular theory, it is thought that these unexpectedfindings can be attributed to, for example, one or more of the followingfeatures of the heat transfer device: the increased contact surfacebetween the heat transfer region of the heat transfer device and thepatient's anatomy; the reduction in heat transfer resistance across thedevice achieved by manufacturing heat transfer devices of the presenttechnology with thinner wall thicknesses; the superior heat transfercharacteristics of the materials used to construct the heat transferdevices of the present technology; and the reduction of gastric pressurethrough gastric ventilation.

Following cooling, the set point temperature of the heat transfer mediumwas switched to a warming mode (42° C.).

To further simulate the hypothermia inducing conditions of the operatingroom, the swine was left exposed to the ambient temperature of the room(22° C.), continuously anesthetized with inhalational anesthesia,paralyzed with a non-depolarizing paralytic to prevent shivering, andprovided with a continuous flow of maintenance room temperatureintravenous fluid hydration.

Data from the warming and maintenance phase of the experiment are shownin Table 3. The data in Table 3 demonstrate an initial maintenance ofthe swine body temperature at 33.6° C., followed by a successful safe,gradual increase in body temperature for the duration of the experiment.FIG. 12 shows the total amount of heat transferred, as calculated above,during the warming and maintenance phase of the experiment.

TABLE 3 Operative Temperature Management and Warming Time (min) RectalTemperature (° C.) 0 33.6 5 33.6 10 33.6 15 33.7 20 33.7 25 33.8 30 33.835 33.8 40 33.8 45 33.8 50 33.9 55 33.9 60 33.9 65 33.9 70 33.9 85 34100 34.1 115 34.2 130 34.3 145 34.3 160 34.3 175 34.4 190 34.5 205 34.5

Consequently, the data demonstrate that a heat transfer device of thepresent technology can maintain, and increase, body temperature whilethe patient is exposed to adverse hypothermic conditions of an operatingroom environment.

Example 3 Temperature Modulation

In an experimental model of therapeutic temperature modulation, a heattransfer device according to the present technology was utilized in ananimal study as described below.

Five large swine with masses of between 60 kg and 70 kg were chosen tobest represent the size and average mass of a human patient. The studyutilized methods consistent with current veterinary and USDA standards,with a state-of-the-art, Association for Assessment and Accreditation ofLaboratory Animal Care (AAALAC) International-accredited vivarium.Animal care and handling of was in accord with Office of LaboratoryAnimal Welfare guidance for humane care and use of animals and withregulations outlined in the USDA Animal Welfare Act (9 CFR Parts 1, 2and 3) and the conditions specified in the Guide for the Care and Use ofLaboratory Animals (National Academy Press, Washington D.C., 1996).

Swine were anesthetized with a pre-anesthetic dose of ketamine, thenprovided with anesthesia via inhalational route with isoflurane 2% afterendotracheal intubation achieved with standard endotracheal intubationequipment and technique well known to those skilled in the art.

Temperature was monitored continuously via continuous rectalthermometer, intravascular thermometer, and both vaginal and/or bladderthermometer using temperature-sensing Foley catheters, all placed afteranesthesia and endotracheal intubation.

A commercially available thermal water bath and circulator (GaymarMeditherm III, MTA-7900) was utilized to provide acontrolled-temperature heat transfer medium to the heat transfer device.The specific heat transfer medium utilized was distilled water.Specifications of the commercially available thermal water bath andcirculator are as follows:

Size: 37″h×14″w×18¾″d (94 cm×36 cm×46 cm)

Weight: Empty: 121 lbs. (54.9 kg), Full: 141 lbs. (64.0 kg)

Material: Aluminum shell, 16-gauge steel chassis

Flow Rate: 17 gph per minute

Power: 120 VAC, 60 Hz, 11.5 amps

Electrical Cord: 15 ft. (4.6 m) power cord (16/3 SO), hospital-gradeplug

Temperature Settings: Manual: Water temperature selection range 4 to 42°C. (39.2 to 107.6° F.)

Automatic: Patient temp. selection range 30 to 41° C. (86 to 105.8° F.)

Code: UL416 and CSA C22.2, EMC meets EN60601-1-2

After successful anesthesia and endotracheal intubation of the swine,the heat transfer device was connected to the external thermal waterbath and circulator which was then powered on to initiate the flow ofheat exchange medium (distilled water). The heat transfer device wasthen lubricated with a biocompatible lubricant and introduced into theesophagus of the swine using standard esophageal intubation techniquewell known to those skilled in the art. No stylets or additionaltechniques to enhance rigidity of the heat transfer device werenecessary to allow proper placement. An external measurement of thedistance from oropharyngeal opening to xiphoid process served as anindicator to which the depth of the heat transfer device was inserted.Confirmation of proper depth of insertion was obtained by successfulauscultation of stomach gurgling upon injection of 20 mL of air,aspiration of gastric contents through the gastric lumen of the heattransfer device, and x-ray fluoroscopy demonstrating presence of theradio-opaque stripe and tip in the stomach.

Starting from baseline temperature measured prior to preparation, swinetemperature was reduced by 4° C. by setting the external chiller to runin an automatic mode, with set point that was 4° C. below the baselinetemperature. At 24 hours after initiation of cooling, a rewarmingprotocol was initiated, in which the external heat exchanger was set toa warming mode, while swine temperature was gradually allowed to rewarmat a rate of approximately 0.5° C. per hour. Upon surpassing a goaltemperature of 36° C., recovery from anesthesia was initiated, and eachswine was then monitored post recovery for periods of between 3 and 14days.

A representative plot of temperature versus time is shown in FIG. 13.Throughout the entire protocol, no evidence of thermoregulatoryshivering was seen, and therefore no muscular paralysis medications wererequired, and no medications commonly utilized to treat shivering (suchas meperidine, dexmedetomidine, midazolam, fentanyl, ondansetron, ormagnesium sulfate) were required.

Existing methods to control and modify patient temperature typicallydemonstrate significant variation around goal temperature duringtreatment, with up to plus or minus 1.3° C. variance from goaltemperature seen in some cases. Inadvertent increases above the goaltemperature lessen the therapeutic benefit of hypothermia. Inadvertentovercooling can result in significant complications, including cardiacarrhythmias, coagulopathy, and an increased rate of infection. Incontrast, devices of the present technology provided the surprising andunexpected benefit of reduced variation around the goal temperaturethroughout the steady-state of the treatment protocol. Variation aroundthe goal temperature fell far below that which is demonstrated by otherdevices, and in fact remained for almost the entire protocol within plusor minus 0.1° C. of goal temperature.

During the cooling process, temperature measurements were performedevery 15 minutes initially, and then every 30 minutes once steady statewas reached. The rate of temperature reduction ranged from 0.8° C./hourto as fast as 2.4° C./hour, with an average of 1.4° C./hour. The rate oftemperature reduction was as fast as 703 kJ/hour, with an average of 410kJ/hour. Thus, it was unexpectedly and surprisingly observed that thecooling rate achieved with a heat transfer device of the presenttechnology is greater than that achieved with many other devices andthat the methods and devices of the present technology extract more heatper unit time than many other devices.

During the warming process, temperature measurements were performedevery 15 minutes. As can be seen in the figure, at each 15 min.interval, the rate of temperature increase ranged from zero to as highas 1.2° C./hour, with an average of 0.39° C./hour. Thus, it wasunexpectedly and surprisingly observed that the warming rate achievedwith a heat transfer device of the present technology is greater thanthat achieved with many other devices and that the methods and devicesof the present technology impart more heat per unit time than many otherdevices.

Specific Embodiments

The methods described herein can be illustrated by the followingembodiments enumerated in the numbered sentences that follow:

1. A method for inducing systemic hypothermia comprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

2. The method of sentence 1, wherein the heat transfer device includes adiscrete heat transfer region and the heat transfer region is confinedto the esophagus.

3. The method of sentence 1, further comprising cooling the medium to atemperature below normothermia.

4. The method of sentence 1, further comprising maintaining the patientin a state of hypothermia for at least two hours.

5. The method of sentence 1, further comprising monitoring at least onephysiological parameter of the patient.

6. The method of sentence 5, wherein the at least one physiologicalparameter is body temperature.

7. The method of sentence 6, further comprising maintaining the bodytemperature below about 34° C.

8. The method of sentence 7, further comprising maintaining the bodytemperature between about 32° C. to about 34° C.

The devices described herein can be illustrated by the followingembodiments enumerated in the numbered sentences that follow:

1. An esophageal heat transfer device comprising:

(a) a plurality of lumens configured to provide a fluid path for flow ofa heat transfer medium;

(b) a proximal end including an input port and an output port;

(c) a distal end configured for insertion into an esophagus of apatient.

2. The heat transfer device of sentence 1, further comprising a hollowtube having a distal end configured to extend into a stomach of thepatient.

3. The heat transfer device of sentence 1, further comprising ananti-bacterial coating.

4. The heat transfer device of sentence 1, further comprising anexpandable balloon.

The methods described herein can be illustrated by the followingembodiments enumerated in the numbered sentences that follow:

1. A method for treating or preventing injury caused by an ischemiccondition comprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

2. A method for treating or preventing ischemia-reperfusion injurycomprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

3. A method for treating or preventing neurological injury comprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

4. The method of sentence 3, wherein the neurological injury isassociated with stroke, traumatic brain injury, spinal cord injury,subarachnoid hemorrhage, out-of-hospital cardiopulmonary arrest, hepaticencephalopathy, perinatal asphyxia, hypoxic-anoxic encephalopathy,infantile viral encephalopathy, near-drowning, anoxic brain injury,traumatic head injury, traumatic cardiac arrest, newbornhypoxic-ischemic encephalopathy, hepatic encephalopathy, bacterialmeningitis, cardiac failure, post-operative tachycardia, or acuterespiratory distress syndrome.

5. The method of sentence 4, wherein the stroke is ischemic stroke.

6. A method for treating or preventing cardiac injury comprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

7. A method for treating myocardial infarction comprising:

inducing mild therapeutic hypothermia.

8. A method for treating stroke comprising:

inducing mild therapeutic hypothermia.

9. A method for treating traumatic brain injury comprising:

inducing mild therapeutic hypothermia.

10. A method for treating Acute Respiratory Distress Syndromecomprising:

inducing mild therapeutic hypothermia.

11. The method of any one of sentences 7-10, wherein the hypothermia issystemic hypothermia.

12. The method of any one of sentences 7-10, wherein the hypothermia isinduced via esophageal cooling.

13. The method of any one of sentences 7-10, further comprisingmaintaining the patient in a state of hypothermia for at least twohours.

14. The method of sentence 13, further comprising maintaining thepatient in a state of hypothermia for at least twenty-four hours.

15. The method of sentence 14, further comprising maintaining thepatient in a state of hypothermia for at least seventy-two hours.

16. The method of any one of sentences 7-10, further comprisingmonitoring at least one physiological parameter of the patient.

17. The method of sentence 16, wherein the at least one physiologicalparameter is body temperature.

18. The method of sentence 17, further comprising maintaining the bodytemperature below about 34° C.

19. The method of sentence 18, further comprising maintaining the bodytemperature between about 32° C. to about 34° C.

20. The method of sentence 12, further comprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

21. A method for treating cardiac arrest comprising:

inducing systemic hypothermia via esophageal cooling.

22. The method of sentence 21, further comprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

The methods and devices described herein can be illustrated by thefollowing embodiments enumerated in the numbered sentences that follow:

1. A device for cooling or warming at least one portion of a patient'sbody, comprising:

a heat transfer device including a proximal end, a distal end, and atleast one flexible tube extending therebetween;

the proximal end including a heat transfer medium input port and a heattransfer medium output port;

the distal end configured for insertion into an orifice of a patient;

the at least one flexible tube defining an inflow lumen and an outflowlumen;

the lumens configured to provide a fluid path for flow of a heattransfer medium;

a supply line connected to the input port; and

a return line connected to the output port.

2. The device of sentence 1, wherein the heat transfer medium is acooling medium.

3. A method of using the device of sentence 2 to treat or prevent injurycaused by an ischemic condition comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

4. A method of using the device of sentence 2 to treat or preventischemia-reperfusion injury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

5. A method of using the device of sentence 2 to treat or preventneurological injury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

6. A method of using the device of sentence 2 to treat or preventcardiac injury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

7. A method of using the device of sentence 2 to treat myocardialinfarction comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

8. A method of using the device of sentence 2 to treat strokecomprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

9. A method of using the device of sentence 2 to treat traumatic braininjury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

10. A method of using the device of sentence 2 to treat AcuteRespiratory Distress Syndrome comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing the distal end into an esophagus;

initiating flow of a cooling medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient.

11. The method of any one of sentences 3-10, further comprising coolingthe medium to a temperature below normothermia.

12. The method of any one of sentences 3-10, further comprisingmaintaining the patient in a state of hypothermia for at least twohours.

13. The method of sentence 12, further comprising maintaining thepatient in a state of hypothermia for at least twenty-four hours.

14. The method of sentence 13, further comprising maintaining thepatient in a state of hypothermia for at least seventy-two hours.

15. The method of any one of sentences 3-10, further comprisingmonitoring at least one physiological parameter of the patient.

16. The method of sentence 15, wherein the at least one physiologicalparameter is body temperature.

17. The method of sentence 16, further comprising maintaining the bodytemperature below about 34° C.

18. The method of sentence 17, further comprising maintaining the bodytemperature between about 32° C. to about 34° C.

The methods described herein can be illustrated by the followingembodiments enumerated in the numbered sentences that follow:

1. A method for controlling core body temperature in a patientcomprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a heat transfer medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient tocontrol core body temperature in the patient.

2. The method of sentence 1, wherein the heat transfer device includes adiscrete heat transfer region and the heat transfer region is confinedto the esophagus.

3. The method of sentence 1, further comprising cooling the medium to atemperature below normothermia.

4. The method of sentence 1, further comprising warming the medium to atemperature above normothermia.

5. The method of sentence 1, further comprising maintaining the patientin a state of hypothermia for at least two hours.

6. The method of sentence 1, further comprising maintaining the patientat normothermia for at least two hours.

7. The method of sentence 1, further comprising monitoring at least onephysiological parameter of the patient.

8. The method of sentence 7, wherein the at least one physiologicalparameter is body temperature.

9. The method of sentence 1, further comprising maintaining the bodytemperature below about 34° C.

10. The method of sentence 1, further comprising maintaining the bodytemperature between about 32° C. to about 34° C.

11. The method of sentence 1, further comprising maintaining the bodytemperature at about 37° C.

The methods described herein can be illustrated by the followingembodiments enumerated in the numbered sentences that follow:

1. A method for operative temperature management comprising:

inserting a heat transfer device into an esophagus of a patient, whereinthe heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a heat transfer medium along the fluid path; and

circulating the medium along the fluid path for a time sufficient tomanage core body temperature in the patient.

2. The method of sentence 1, further comprising maintaining the patientin a state of hypothermia for at least two hours.

3. The method of sentence 1, further comprising maintaining the bodytemperature below about 34° C.

4. The method of sentence 1, further comprising maintaining the bodytemperature between about 32° C. to about 34° C.

5. The method of sentence 1, further comprising maintaining the patientin a state of normothermia for at least two hours.

6. The method of sentence 1, further comprising maintaining the bodytemperature at about 37° C.

7. The method of sentence 1, further comprising monitoring at least onephysiological parameter of the patient.

8. The method of sentence 7, wherein the at least one physiologicalparameter is body temperature.

The devices described herein can be illustrated by the followingembodiments enumerated in the numbered sentences that follow:

1. An esophageal heat transfer device comprising:

(a) a plurality of lumens configured to provide a fluid path for flow ofa heat transfer medium;

(b) a heat transfer region configured for contacting esophagealepithelium of a patient;

(c) a proximal end including an input port and an output port;

(d) a distal end configured for insertion into an esophagus of apatient.

2. The heat transfer device of sentence 1, further comprising a hollowtube having a distal end configured to extend into a stomach of thepatient.

3. The heat transfer device of sentence 1, wherein the heat transferregion is capable of contacting substantially all of the esophagealepithelium.

4. The heat transfer device of sentence 1, wherein the heat transferregion comprises a semi-rigid material.

5. The heat transfer device of sentence 1, wherein the device is capableof cooling at a rate of about 1.2° C./hr to about 1.8° C./hr.

6. The heat transfer device of sentence 1, wherein the device is capableof cooling a mass at a rate of about 350 kJ/hr to about 530 kJ/hr.

7. The heat transfer device of sentence 6, wherein the device is capableof cooling a mass at a rate of about 430 kJ/hr.

8. The heat transfer device of sentence 1, wherein the device includes aheat transfer region with a surface area of at least about 100 cm².

9. The heat transfer device of sentence 8, wherein the heat transferregion has a surface area of about 140 cm².

The devices and systems described herein can be illustrated by thefollowing embodiments enumerated in the numbered sentences that follow:

1. A system for cooling or warming at least one portion of a patient'sbody, comprising:

a heat transfer device including a proximal end, a distal end, and atleast one semi-rigid tube extending therebetween;

-   -   the proximal end including a heat transfer medium input port and        a heat transfer medium output port;    -   the distal end configured for insertion into an orifice of a        patient;    -   the at least one semi-rigid tube defining an inflow lumen and an        outflow lumen;    -   the lumens configured to provide a fluid path for flow of a heat        transfer medium;

a supply line connected to the input port; and

a return line connected to the output port.

2. The system of sentence 1, wherein the orifice is an esophageal lumen.

3. The system of sentence 2, wherein the heat transfer device comprisesa heat transfer region capable of contacting substantially all of theesophageal epithelium.

4. The system of sentence 1, further comprising a hollow tube having adistal end configured to extend into a stomach of the patient.

5. The heat transfer device of sentence 1, wherein the device is capableof cooling at a rate of about 1.2° C./hr to about 1.8° C./hr.

6. The system of sentence 1, wherein the device is capable of cooling amass at a rate of about 350 kJ/hr to about 530 kJ/hr.

7. The system of sentence 6, wherein the device is capable of cooling amass at a rate of about 430 kJ/hr.

8. The system of sentence 1, wherein the device includes a heat transferregion with a surface area of at least about 100 cm².

9. The system of sentence 8, wherein the heat transfer region has asurface area of about 140 cm².

The devices and systems described herein can be illustrated by thefollowing embodiments enumerated in the numbered sentences that follow:

1. A system for controlling core body temperature of a subject,comprising:

a heat transfer tube insertable within the esophagus of the subject,wherein the tube is configured to contact the epithelial lining of theesophagus;

an external heat exchanger containing a heat transfer fluid;

a pump for flowing the heat transfer fluid through a circuit within theheat transfer tube;

a heat transfer element in contact with the external heat exchanger; and

a sensor for detecting a parameter and generating a signalrepresentative of the parameter, wherein the signal is transmitted to amicroprocessor to control (i) the flow heat transfer fluid within thecircuit or (ii) the temperature of the heat transfer fluid.

2. The system of sentence 1, wherein the sensor is a temperature sensorpositioned distal to the heat transfer tube and configured to generate asignal representing the core body temperature of the subject.

3. The system of sentence 2, wherein the microprocessor receives atarget temperature input and responds to the signal from the temperaturesensor with a proportional integrated differential response to controlthe rate at which the subject approaches the target temperature.

4. The system of sentence 1, wherein the sensor is a bubble detector andconfigured to generate a signal representing the presence of air in thecircuit.

5. The system of sentence 1, wherein the heat transfer tube comprises aheat transfer region capable of contacting substantially all of theesophageal epithelium.

6. The system of sentence 1, further comprising a hollow tube having adistal end configured to extend into a stomach of the patient.

7. The system of sentence 1, wherein the device is capable of cooling ata rate of about 1.2° C./hr to about 1.8° C./hr.

8. The system of sentence 1, wherein the device is capable of cooling amass at a rate of about 350 kJ/hr to about 530 kJ/hr.

9. The system of sentence 1, wherein the device is capable of cooling amass at a rate of about 430 kJ/hr.

10. The system of sentence 1, wherein the device includes a heattransfer region with a surface area of at least about 100 cm².

11. The system of sentence 10, wherein the heat transfer region has asurface area of about 140 cm².

The presently described technology is now described in such full, clear,concise and exact terms as to enable any person skilled in the art towhich it pertains, to practice the same. It is to be understood that theforegoing describes preferred embodiments of the technology and thatmodifications may be made therein without departing from the spirit orscope of the invention as set forth in the appended sentences.

1. A method for controlling core body temperature in a patientcomprising: positioning a heat transfer device within the patient'sesophagus, wherein the heat transfer device includes one or more lumensproviding a fluid path for flow of a heat transfer medium; initiatingflow of a heat transfer medium along the fluid path; and circulating theheat transfer medium along the fluid path for a time sufficient tocontrol core body temperature without provoking a shivering response inthe patient.
 2. The method of claim 1, wherein the device comprises aninput port for receiving the heat transfer medium from a source and anoutput port that allows the heat transfer medium to return to thesource.
 3. The method of claim 1, wherein the heat transfer medium iswater, saline, propylene glycol, ethylene glycol, or a mixture thereof.4. The method of claim 1, wherein the core body temperature of thepatient is maintained between about 34° C. and about 37° C.
 5. Themethod of claim 1, wherein the core body temperature of the patient ismaintained between about 34° C. and about 37° C. for at least two hours.6. A method for treating or preventing ischemia-reperfusion injury in apatient comprising: positioning a heat transfer device within thepatient's esophagus, wherein the heat transfer device includes one ormore lumens providing a fluid path for flow of a heat transfer medium;initiating flow of a heat transfer medium along the fluid path; andcirculating the heat transfer medium along the fluid path for a timesufficient to induce hypothermia or maintain normothermia; wherein themethod does not include concomitant administration of anti-shiveringinterventions.
 7. The method of claim 6, wherein the device comprises aninput port for receiving the heat transfer medium from a source and anoutput port that allows the heat transfer medium to return to thesource.
 8. The method of claim 6, wherein the heat transfer medium iswater, saline, propylene glycol, ethylene glycol, or a mixture thereof.9. The method of claim 6, wherein hypothermia is maintained for at leasttwo hours.
 10. The method of claim 6, wherein normothermia is maintainedfor at least two hours.
 11. An esophageal heat transfer devicecomprising: a distal end configured for insertion into a nostril ormouth of a patient; a heat transfer region configured to directlycontact esophageal epithelium of the patient, wherein the heat transferregion does not include a balloon or partially inflatable lumen; aninput port for receiving a heat transfer medium from a source; and anoutput port that allows the heat transfer medium to return to thesource.
 12. The device of claim 11, wherein the heat transfer region hasa surface area of at least about 100 cm².
 13. The device of claim 11,further comprising a gastric access tube allowing for removal of gastriccontents.
 14. The device of claim 11, further comprising a temperaturesensor.
 15. The device of claim 11, further comprising a pressure sensor16. An esophageal heat transfer device comprising: a distal endconfigured for insertion into a nostril or mouth of a patient; a heattransfer region having a diameter of about 1.0 to about 2.0 centimeters;an input port for receiving a heat transfer medium from a source; and anoutput port that allows the heat transfer medium to return to thesource.
 17. The device of claim 16, wherein the heat transfer region hasa surface area of at least about 100 cm².
 18. The device of claim 16,further comprising a gastric access tube allowing for removal of gastriccontents.
 19. The device of claim 16, further comprising a temperaturesensor.
 20. The device of claim 16, further comprising a pressuresensor.